Dave Messina

General Partner, @Pioneer_Fund leading the Future of Health Fund. Co-founded @CofactorGenomic. @YCombinator alum. previously Human Genome Project.

[Dave Messina @DaveMessina]

Excited for me and @pioneer_fund to be backing this team!

[James Fong @jamesfong]

🧬 FinalDose is building the first programmable drug. A single smart molecule you can load with any diseased genetic code, and it searches out and destroys cells the moment it recognizes that DNA. Starting with cancer.

For sixty years, drug discovery has chased proteins. The problem is that roughly 85% of disease drivers have no druggable protein at all, because disease usually starts in the DNA, not the protein downstream of it. FinalDose goes straight for the DNA. Their molecule scans the genome for a target sequence, and when it finds a match inside a diseased cell, a structural change triggers a kill switch that destroys that cell while leaving healthy neighbors untouched. Same molecule, new guide, new drug, which means each new mutation target becomes a new drug asset from the same core platform. They're already seeing selective activation in cell line data.

https://t.co/0szdT8QyTM

Jeff Liu, DPhil, Li-Yao Huang, and Steven Lin are all Oxford PhDs in Oncology, Biochemistry, and Computational Biology who have known each other for 7+ years. They bring a track record across diagnostics and construct engineering. @pioneer_fund can't wait to see what breakthroughs they uncover!

[Eric Topol @EricTopol]

Another major advance vs cancer! @ASCO #ASCO26
Personalized neoantigen mRNA vaccine 5 year follow-up vs metastatic melanoma reduced recurrence and death by 49% (on top of Keytruda)
https://t.co/NadITTYIT2

[Joseph Younis, MD @YounisJoseph]

The breakthrough isn’t the median survival rate doubling, it’s the fact that they’ve finally managed to create a drug that can target the RAS(on) state, rather than selective KRAS mutations. This makes it the first multi selective RAS inhibitor that’s clinically proven to work. The implications are huge. KRAS mutations are found in:
1. 90% of pancreatic cancers
2. 40-50% of colorectal
3. 20-40% lung
4. 19-23% of ALL cancers

[Dave Messina @DaveMessina]

Health/bio is the greatest investment opportunity of this decade.

[🐊ZK For Tre🐊 @ZKForTre]

I feel like I am often too negative here (sometimes for good reason), but I want to give people a sense for why we might be 10 years away from a paradigm shift in cancer outcomes.

This year, we have proof of concept for all of the following:

mRNA vaccine success against low antigen burden cancers (i.e. PDAC): https://t.co/3mCykQLKDH

Immune activation by non-specific antigens (COVID Vaccines): https://t.co/MmoJZhpG9n

Successful drugging of undrugable driver genes: https://t.co/SR2lnKnJJz

Successful drugging of hard to drug driver genes: https://t.co/Ize0nigQFo (this presentation data was admittedly noisy so I'm holding off on this for now),

Next generations target-specific CAR-T/T cell engagers: https://t.co/9XlCUVZTJN

Antibody-drug conjugates for more targeted therapy: https://t.co/V8wS1Agc9r
https://t.co/yD63glK6jY

Melanoma mortality rates cut in half (not new but new data supporting durable treatment effect): https://t.co/DUscZg5qow

Transformative improvements for patients with Multiple myeloma: https://t.co/aMbfjM7xIg
https://t.co/gKNl97UKVy
https://t.co/qcFrAENQtR

GLP1s as potential anti-cancer agents (lots of mechanisms possible here, no clinical data, so hold off on any conclusions and appreciate the multiple reasons why this may not pan out-- i.e. cachexia concerns): https://t.co/to6JH78Et5

And, of course, AI for diagnostic radiology.

Still a long, long way to go, especially for the average, non-trial-enrolling patient. But there is reason for hope in the coming years for cancers that were death sentences as recently as 5 years ago. All of this on top of proven efficacy of checkpoint inhibitors, existing antibodies and small molecules, and the emerging technologies like adoptive cell therapies and tumor-specific mRNA vaccines.

[Eric Topol @EricTopol]

There hasn't previously been a treatment vs pancreatic cancer this successful. Striking improved (a > doubling) survival results @NEJM and @ASCO today with daraxonrasib, which also became available via an FDA approved early access program and began shipping to physicians this week @RevMedicines
https://t.co/e04jqJMPw0

[roon @tszzl]

the greatest whitepill of all is that local minima are rare in high dimensional spaces

[Rod Wong, MD @docrodwong]

a standing ovation for daraxonrasib at asco. over 40k oncologists, entrepreneurs, investors, and patient advocates together celebrating revmed's breakthru in the fight against pancreatic cancer. u never forget these moments. it's what innovation is all about.

[Coffee with One 🇺🇸 @coffeewithone]

Watched a customer spend 6 hrs straight in @octolane today.
Years of building AI CRM taught us one thing worth saving:

1. There's a specific number that unlocks activation
2. There's a specific feature set + specific numbers that unlocks retention

When you find both of them, there's no going back.

But how did we find ours?

🚀 Activation: Look at every user who converted to paid. What's that one behavior they all did in week 1 that churned users didn't? That's gonna be your activation event. Now your job to find the smallest number of repetitions that predicts conversion.

🔄 Retention: Research your month 2 retained users. What combination of features did they use in weeks 2 to 4 that churned users skipped? That's your retention game will surface.

Sounds obvious but I promise you It's not gonna be when you're in it.

We cracked activation first. Then retention. Both took painful iteration, shipping, breaking, rebuilding, shipping again. It was an excruciating process for us where we were not sure if we're getting closer or just running in circles. Until suddenly you are, and you can't unsee it.

Teams are now migrating from HubSpot, Pipedrive, and Attio to Octolane. We did zero outbound and all word of mouth.

Because the agent-first economy lets us solve the edges incumbents can't.

Founders, what number unlocked activation for you?

[Ankit Gupta @agupta]

we're funding a lot of PhD researchers at YC these days

super pumped that we're hosting a reading group at the og YC office near Stanford and will be putting the videos on youtube. More of this to come!

[TBPN @tbpn]

"I think what tech people misunderstand is just the size of the TAM in pharma."

@zebulgar says capital will rotate into pharma after AGI:

"Anthropic is at what, a $60B run rate? Keytruda, the drug that Merck did in 2019, that one drug's topline is $25B in revenue. Just that one drug."

"By the way, once there's AGI, what do you think everybody's going to be focused on afterwards? Everybody's just going to want to live forever. Where do you think the capital is going to rotate into? It's going to rotate into longevity, therapeutics, and manufacturing."

From his appearance on the show earlier this month.

[Dave Messina @DaveMessina]

@coffeewithone @octolane Excited to be a small part of the journey with you, One!

[Dave Messina @DaveMessina]

@coffeewithone Huge congrats to @octolane !

[Coffee with One 🇺🇸 @coffeewithone]

Octolane started by watching my mom.

Single mom. Four sons. Seven days a week. No CRM. But she remembered every customer and every promise.

I was Mintlify's first intern working in SF. One day I looked at the Salesforce tower and thought: my mom didn't need a CRM. What if no one did?

Dropped out of Duke. Started Octolane with my best friend @halim__rafi and a team of 5, engineers twice our age who left real jobs to bet on us. Working from coffee shop to coffee shop, 7 days a week, spending as little as possible.

Today, after onboarding 1,000+ companies manually, @octolane - The Self-driving AI CRM is generally available.

You talk to Octolane like a co-founder. It figures things out and does the work end to end. Because the best CRM is no CRM.

→ 10,000+ action types - the largest action library in any CRM
→ 200+ integrations + MCP server (works inside Claude, Cursor, ChatGPT)
→ Multi-agent system: agents talk to each other to run your pipeline
→ Self-improving sales playbook that compounds with every deal

Give it a shot today. Break the product. Let us know.

My number: 628-285-1600. Text me for a launch-day coupon. First 20 calls, I'll onboard you myself.

🌉 Built in San Francisco | Thanks to @ycombinator

[Tim Suzman @TimSuzman]

Search FOR AI will be much bigger than search for humans.

One human, one search at a time. Click. click.

One agent will sometimes want to run 1,000,000 searches in parallel.

[Peter Suzman @Biomaven]

@pioneer_fund @DaveMessina

[Jared Friedman @snowmaker]

OpenAI is offering $2M in tokens for every company in the summer '26 batch.

We're not sure if we'll do this again, so we've extended the deadline to apply to the summer batch to May 25.

[Tim Suzman @TimSuzman]

"This is probably what it was like to talk to the Google founders at the very beginning of Google."

[Pioneer @pioneer_fund]

2 years after we invested in @ExaAILabs seed round, they reframed what they were doing.

Search using LLMs --> Search *for* LLMs

Pioneer immediately invested again, 6x our original investment amount.

[Pioneer @pioneer_fund]

Managing Partner @TimSuzman on our seed investment in Exa, which just raised from a16z at a $2.2B valuation.

[Tim Suzman @TimSuzman]

Exa raises $250M @ $2.2 Billion led by a16z!

Congratulations to @ExaAILabs on behalf of the whole @pioneer_fund team!