Jesse Chen

Passionate about drug discovery and development. Founder and CEO of Fortitude Biomedicines. Opinions are my own.

[Jesse Chen @jessechen7]

💯

[soria @jsoriamd]

🧬 ADC innovation requires payload diversification—not just target diversification.
• 🔄 The ADC pipeline is increasingly dominated by TOP1 inhibitor payloads, raising concerns about resistance mechanisms and overlapping toxicities.
• 💡 Trastuzumab deruxtecan illustrates that historically unsuccessful cytotoxics can become effective payloads when redesigned for antibody-mediated delivery.
• 🎯 Future payload selection should prioritize pharmacologic behavior—proliferation-restricted activity, favorable pharmacokinetics, sustained intracellular target engagement, and controlled bystander effects—rather than maximal in vitro potency.
• 🔬 Legacy cytotoxics (e.g., antifolates, nucleoside analogs), degraders, immune-stimulants represent an underexplored source of mechanistically distinct ADC payloads.
• 🚀 Broadening payload diversity may expand therapeutic opportunities, delay class-wide resistance, and define the next generation of precision ADCs.
https://t.co/d5RQgchvdw

[Jesse Chen @jessechen7]

It’s a roulette table until we bring back precision oncology where novel payloads like #DAC can guide biomarker driven patient selection and combo strategies

[Antonio Giordano, MD PhD @antgiorda]

#ADC development in #breastcancer is the ultimate roulette table:

🎯 New targets (NECTIN4, B7-H4, HER3…) = single-number bets
🔴�� TROP2 vs HER2 = red or black
⚖️ TOP1i vs MMAE = odd or even

Everyone wants the jackpot. Few predict the winning number.
#MaTOS

[Jesse Chen @jessechen7]

Finally a rational, disciplined, and grounded thesis by @LifSciVC

https://t.co/FZ33gylDjy

[Woo Lab @thewoolab]

We’re popping the champagne prior to New Year’s because our work on how PCMT1 enzymatically forms the CRBN degron is officially out in @nchembio 🥂!! Congrats to Zhenguang (@Zhenguang4), Wenqing, Ethan (@EthanYFeng), Shiyun, and all the authors! 🎉💜🍾 https://t.co/8OHh9uNDPK

[Jesse Chen @jessechen7]

@Mykalt45 @CrossBridgeBio Very cool congrats!

[Woo Lab @thewoolab]

Check out our lab's newest pub, live in ACS ChemBio! We report interesting CRBN-independent activities of N-alkylated lenalidomide derivatives, or "capped imides." Congrats to Farah and all of the authors! 🥳💐
https://t.co/Q1j0l02OyP

[Jesse Chen @jessechen7]

@elonmusk Hi Elon there’s sometime that bothers me a lot. If I just want to see the relies I need to click the post to expand instead of the relies icon. Can you change it so that when I click replies, I can actually see the list of replies and at the bottom I can type in the reply?

[Lightspeed @lightspeedvp]

Lightspeed-backed @Triana_Bio has announced a new research collaboration with @pfizer to discover molecular glue degraders for several disease areas, including cancer. Congratulations to Co-Founders @Jessechen7 and @KodadekThomas for their leadership in addressing challenging diseases by prioritizing the discovery of hard-to-treat molecules.

In this partnership, TRIANA will lead the initial stages of drug discovery and design, while Pfizer will have the option to license the drug candidates and carry them through preclinical and clinical studies.

Learn more via @Endpts: https://t.co/Px81DNWw12

[Jesse Chen @jessechen7]

@elonmusk So true!

[Jesse Chen @jessechen7]

@LifeSciVC Love #3! Too late for me to think about dedifferetiation!

[Bernat Olle 🇺🇦 @bernatolle]

There is only one thing harder to get from an investor than💰: candid feedback

I wrote some thoughts here @timmermanreport 🧵 including rationalizations investors give themselves to avoid giving it & how entrepreneurs can improve odds of getting it /1

https://t.co/ygCciHJZsc

[Peter Kolchinsky @PeterKolchinsky]

This thanksgiving, among all else, I'm going to be really grateful to all biopharma executives who read this article and arm their ex-US HEOR teams with the creativity and budgets of their US commercial marketing team to develop a unified campaign against death math.

https://t.co/Ut7FKg0Gwy

That won't make sense to many, but it might to a few... maybe you... in which case it's you whom I'm addressing.

Consider how Bernie Sanders is convening an angry panel on why the US pays more than Europe for medicines, certain that it means that the US is overpaying. He wants more price controls. His misdiagnosis of the problem isn't academic. The IRA is proof of that.

By paying much less for new medicines, many countries are freeriding on the back of the US's market-based investments into new medicines. But only a few, notably the UK, are like a scorpion stinging the turtle in the head to talk the US into thinking that it's just not worth swimming. They risk downing everyone.

In this case, their venom is conventional CEA math. Instead of just saying "we don't feel like doing our fair share of the paddling", they are doing math that ignores much of what makes medicines valuable (e.g. that they can go generic, they benefit caregivers, etc) to claim that they aren't worth much. It's not even smart of them to do this. A smart freerider would not be making the one they are freeriding off of feel stupid for helping everyone else. It's they like reading books inexpensively at a library, they really shouldn't talk everyone else out of buying books; because if everyone exclusively used the library, they would all look around one day and wonder why they aren't seeing any new books on the shelves. Yup, someone has to support the publishing industry.

The US can't freeride off anyone. If it gives up on market-based pricing for patent-defined periods of time, that's it. We and our kids will be limited to the medicines we have now and rising hospital costs.

It would take a tiny fraction of biopharma's US marketing brains and muscle to come up with a campaign to remove the scorpion's stinger (e.g. No Patient Left Behind has been nurturing the seeds of that campaign, check out the Value Flower video on its website).

If we don't remove that stinger or render the US immune to its venom, then someday all the heads of US Commercial operations at every biopharmas find that their talents are no longer needed... for the US will have negated all marketing efforts with simple measures like... the IRA 9y penalty... turned into a 5 year penalty... and expanded to commercial market... which extinguishes all R&D investment... and means that there won't be any new drugs to sell.

We've compartmentalized so many functions that I very much worry that US commercial folks have no idea how their jobs are being undermined by what is being exported to the US from Europe nor how effectively they could partner with their HEOR colleagues to... build pedestals for our products instead of guillotines. (If that last bit is confusing, read the article).

We all have a stake in this. This isn't something that just people in the drug industry should care about. If we don't invent new medicines to stay healthy, productive, and our of hospitals, then we'll only end up spending more in the worst pay possible, suffering in hospitals and nursing homes. And unlike with medicines, Europe can't freeride off US investments in nursing homes... when those bills come, every country has to pay their share or watch their citizens wither in the most undignified way imaginable.

@novonordisk @Lilly @biogen @pfizer @Amgen @PhRMA @IAmBiotech #scorpions :( #turtlesareawesome :) @Regeneron @moderna_tx @BioMarin @argenxglobal @GSK @AstraZeneca @TakedaPharma @OtsukaUS @EisaiUS @VertexPharma @NPLB_org #sorryformissingafew @SenateHELP @GileadSciences @sanofi @Roche @genentech @AscendisPharma @ImmunoGenInc @RhythmPharma @npcnow @NPR @thebiotechclub @NucleateHQ @Merck @bmsnews

[Jesse Chen @jessechen7]

@PeterKolchinsky @stuartbuck1 @VivekSubbiah @matthewherper @NatureMedicine Well said Peter! I remember @VivekSubbiah mentioned in one podcast that only one or two out of 48 between 2009-2022 were withdrawn. Most recent one Exkivity. Almost all got full approval. So the current system works extremely well!

[Jesse Chen @jessechen7]

@historyinmemes @TomBrady no question GOAT all sports combined: athleticism, achievement and longevity of a player’s career

[Jesse Chen @jessechen7]

@LifeSciVC Looks like you have a better shot than getting a @taylorswift13 ticket!

[TRIANA Bio @Triana_Bio]

Great effort by TRIANA scientists with @UNSW to explore novel technologies to discover and characterize molecular glues! https://t.co/4ghRyfusvo

[TRIANA Bio @Triana_Bio]

Welcome to our CBO Reza Mazhari!
https://t.co/zkdAb4ZZIW
#molecularglues #proteindegradation

[Jesse Chen @jessechen7]

@elonmusk Elon can you please elaborate why a few rockets were not firing during the launch? Was it intentional? Congrats as always!🚀🚀🚀🚀🚀

[Jesse Chen @jessechen7]

@D_B_McConnell Agree with @EndriuT

[Avilar Therapeutics @Avilar_Tx]

The Avilar team is seeking a motivated, collaborative cell biologist to join us as a scientist in our goal to develop genuinely transformative medicines that dramatically improve care for patients. Check out the full job description on our website
https://t.co/LpEJKuPkj6