Reed Jobs is easy to like. He’s motormouthed, self-deprecating, prone to video-game analogies, and clearly loves his work. He doesn’t particularly want to discuss the fact that he is Steve Jobs’s son, but he’s not uptight about it, either. When our producer, Maggie, asked if he was on a MacBook for our video call Thursday morning, he didn’t miss a beat: “Are you kidding?”

What he’d much rather talk about is Yosemite, the oncology-focused venture firm he launched in 2023 to, in part, build biotech companies from scratch, out of early academic research, using a mix of philanthropy and outside investment capital. Three years in, Jobs is ambitious about turning Yosemite into a serious player, not just because he wants to win but because he thinks the opportunity in front of him is expanding faster than he expected thanks to AI’s impacts on both drug discovery and clinical trial design.

Among the portfolio companies he’s proudest of are Azalea, born from a grant to Jennifer Doudna’s lab and now in the clinic, and Quarry, a company built with serial founder Craig Crews around a novel therapeutic approach called induced proximity, wherein a drug works by physically dragging a disease-causing protein next to the cell’s own breakdown system (instead of trying to block it directly).

When we last sat down with Jobs at TechCrunch Disrupt nearly three years ago, Yosemite was brand new and biotech was still reeling from its post-pandemic crash. Now, the firm has a team of 17; a cluster of blockbuster drugs are all losing patent protection in roughly the same window, creating all kinds of new opportunities; and AI has gone from a curiosity to, in Jobs’s words, a huge part of what Yosemite does. We caught up on all of it.

This Q&A has been edited for length.

TC: You announced the first close of your second fund earlier in the year, targeting $350 million. What’s the state of the union at Yosemite?

RJ: One of extreme activity right now. We’ve had incredible traction, and we’ve brought on a lot of really important new partners. Yosemite is a unique venture organization for two reasons: we only work in oncology — that’s 40% of biotech — and we like to make our own companies ourselves. We don’t think the cures for cancer are sitting out in pharma waiting to be discovered; we think we need to go make them with new knowledge. To de-risk those ideas early, when they’re still gentle ideas in university labs, we use a little philanthropy in a completely no-strings-attached way. Two of our 20 companies in the first fund came directly out of a grant.

How much of that $350 million is going into companies you’re spinning up yourselves versus companies you’re joining?

About a third goes into companies we’re making ourselves — either our own ideas or ones we build alongside academics, at places like Yale, Berkeley, and Stanford. That takes a lot of time and energy, which is why it’s only a third. The rest goes into companies other people made that we want to join. Separately, 2.5% of the fund’s [assets under management] goes into a donor-advised fund — that’s completely no-strings-attached grant money, plus $1 million a year from our management fees.

It’s early days, but what’s the case you make to prospective LPs on performance relative to other life science VC firms?

It’s extremely early for us, but Yosemite has the ability to create new areas of medicine before other firms get there. My team has pioneered a couple of these: epigenetic gene editing [technology that changes how strongly a gene is expressed, rather than altering the underlying DNA sequence itself], and safe delivery of gene editing to specific cells — a bottleneck for the whole field for the better part of a decade. If you want to be first, and you want to help discover new areas, that’s what we’re going to be best at.

Earlier on, you were worried about how conservative biotech investors had become. Has that changed?

It has, actually. When I launched Yosemite in 2023, the XBI [ETF/index] was still down massively from its 2021 highs and pharma hadn’t gotten acquisitive yet. What’s changed in the last three years: interest rates are better, and pharma is entering its largest patent cliff in history while sitting on record cash reserves from the pandemic. That’s added up to an acquisitive spree over the last eight months or so. We’ve seen huge exits, like Eli Lilly buying Kelonia for $7 billion, and massive wins in antibody drug conjugates. One high-profile one: Revolution Medicines, going after KRAS [one of the most commonly mutated cancer-driving genes, long considered nearly impossible to target with drugs] in pancreatic cancer, has doubled the survival rate for [the most common form of pancreatic cancer] — from 12 to 24 months. That’s only happened in the last year.

Last year you talked publicly about your concerns over proposed NIH cuts.

Unfortunately, there’s still pressure from the federal government, but it’s less of a long-term threat than it was. Last year, for the first time in history, an administration asked for a cut of up to 40% of the NIH budget. For context, the biggest cut that ever happened was 1% in 2009, in response to the global financial crisis, and that cost 7,000 NIH scientists their jobs. Gratefully, the Senate and House — this is extremely bipartisan — totally rejected the 40% cut. This year they came back asking for 12%, still the biggest cut of all time by an order of magnitude, and I expect the same rejection. NIH funding has more than 90% approval. Personally, I think we should go on offense — I’d increase it to something like $100 billion. On a dollar basis, it hasn’t grown in about a decade, so relative to inflation, it’s actually shrunk.

Where is AI already changing healthcare delivery?

American hospitals are some of the most technologically naive places in the economy — there’s still a huge amount done on fax, on floppy disk. One example: call centers, like 911 triage, are expensive to keep open 24/7 and are ripe for AI. There’s also electronic health records, radiology, pathology. But where I get really interested is clinical trials — the biggest cost and time sink in drug development. A Phase 3 cancer trial costs about $260 million, and only one in three succeeds. The biggest cost is patient recruitment and retention. AI could help build a synthetic control arm [a computer-generated stand-in for the untreated comparison group, built from existing patient data], so instead of recruiting a full control group, you only recruit the active arm — that halves the patients you need and massively increases speed. The FDA is leaning into this right now.

What about AI in drug discovery — is it overhyped?

I think it’s a fantastic advancement, for democratizing science and for accelerating things. What AI is doing right now is accelerating a lot of grunt work — not necessarily doing it better, but doing it incredibly fast, with reproducible outcomes.

AI has [also] been great at finding pockets we’ve never been able to hit before. Historically we could only drug about 15% of the genome, because we couldn’t drug proteins interacting with other proteins — the chemistry was too hard. That’s changed in the last couple of years, hand in hand with AI. Take Revolution Medicines: they’re the first to drug KRAS, which for decades had no [natural dent or crevice on its surface for a drug molecule to latch onto and block] — it’s basically a smooth oval, a death star. About 10 years ago, scientists at Amgen found a weird cryptic pocket in it, leading to the first drug against it, Lumakras. It only worked for one specific mutation; what AI has done is find all the other variants we can now target and show creative new ways to block it.

What undruggable targets are your companies going after?

The biggest one of all: p53. We’re going after it with three different companies and several strategies. It’s a tumor suppressor gene — famously, elephants don’t get cancer, and one theory is they have dozens of copies of p53, while humans have just one, which is easily taken out. p53 is the most frequently suppressed gene across human cancers; almost every cancer has to knock it out to exist in the first place. If we could turn it back on, or attack its mutated forms, that’s one of cancer’s Achilles’ heels, and it’s never been done. We think we found something to hit that exposed [marker] across all the different ways p53 gets mutated.

Tell me about Tune Therapeutics.

Tune has been the premier epigenetic editing company in clinical development for the last couple of years, targeting hepatitis B, which affects over 250 million people and is the primary driver of liver cancer. The technology lets us add or remove methyl groups [small chemical tags that attach to DNA and act like a dimmer switch, turning a gene’s activity up or down without changing the gene itself] at specific sites in the liver. Every cell in your body has the same DNA but expresses it differently — think of gray hair: melanin gets methylated and turned off, so your body still makes hair, just less robust. That’s the same process behind aging immune systems and slowing metabolism. Hepatitis B looks foreign to your body, so we’re aiming to methylate and silence the virus itself, the way about 1% of people who spontaneously clear the virus seem to do naturally.

Meanwhile, Histosonics is a device company, which seems unusual for Yosemite.

You’re right, we don’t usually do devices. It’s the first company using histotripsy at scale for liver tumor destruction, using noninvasive therapy — creating small air pockets, then collapsing them to destroy tissue in a very specific area, similar to an ultrasound rather than a CT scan. Their lead programs are in pancreatic and liver tumors — most pancreatic cancer metastasizes to the liver, so it’s a natural pairing. We think this becomes a huge part of therapy for both.

How many companies are in the portfolio now, and any failures yet?

Close to 25 across both funds. Two haven’t worked out for scientific reasons — we tranche these investments against scientific milestones, and since we’re so early, sometimes things fail on the science. That’s what we’d expect.

How do you advise founders weighing a big check from big pharma? You get the funding, but it cuts off other options.

Pharma is a key partner, but founders need to see it as a moving target — priorities shift a lot depending on leadership. After COVID, many pharma companies lost money in infectious disease and moved out of the space entirely — Pfizer, for instance. Staying attuned to who’s actually active in your area is probably the most important thing.

How can founders who want to get in front of you do this?

We have an open door. When we look at grants and companies, we take people’s CVs out of it — I don’t want to know whose idea it is or what title someone holds. We’ve funded Nobel laureate labs and first-time grant recipients, and I’m equally happy with either outcome. We look at every modality — small molecules, radiopharmaceuticals, gene therapy, immunotherapy, AI, digital health. Please email us. Any idea that can affect cancer patients, we want to know about it.

Does storytelling matter as much for biotech founders as in other industries?

Unfortunately, yes — I’ve seen companies with great science fail because of bad storytelling from the CEO. But usually the founder and CEO aren’t the same person. The founder is often the academic — the chief scientist or chief medical officer — and the CEO is a professionalized operator whose job includes raising capital and telling the story. That division of labor works well.

Three years into running Yosemite, what’s been the biggest surprise?

We now have the first trillion-dollar pharmaceutical company, Eli Lilly, because of GLP-1s — the best-selling drug class in the world. We’re also seeing early signs GLP-1s may be protective against neurodegenerative disease and cancer, unrelated to weight loss, because obesity is one of only two “pan-disease” risk factors — the other being smoking — that raise your risk across nearly every disease category. That’s made people look with fresh eyes, fresh ambition, and real capital at huge disease areas that had gone cold. Genes like KRAS, Myc, beta-catenin, and p53 — the pantheon of oncogenes that have evaded us for decades — are now, we think, within reach. I didn’t expect Yosemite to be moving this fast. This time is more important than I realized, which is both scarier and more empowering.

Before you go, what do you make of the longevity industry?

I don’t want to die anytime soon, and longevity is important to me personally. But I don’t think we — or anyone — really knows what we’re talking about yet. Ask a geneticist and they’ll tell you about telomeres; ask an immunologist and they’ll tell you about T cells losing efficacy; ask a metabolomicist and you’ll get a different answer still. There’s no grand unified theory of aging the way there is in physics. I don’t think you “have” a longevity problem — I think your body ages differently across different cell types, and the interaction of all that is what we call aging. Optimizing that per person is exactly what healthcare should be doing, but I don’t know how you turn longevity into a one-size-fits-all business.

Open source AI is booming, according to Hugging Face CEO Clem Delangue. The company has grown into something like a GitHub for AI in recent years, where AI builders can share and download open models and datasets, now used by roughly half the Fortune 500. Delangue has seen the same story play out again and again: companies start out on frontier APIs, but as they scale, the costs push them towards open source models. 

On this episode of TechCrunch’s Equity podcast, Rebecca Bellan talked to Delangue about why the open vs closed source fight matters in the wake of Anthropic’s halted Fable release, and why he’s worried about the possibility that a handful of big companies could end up controlling everything. 

Subscribe to Equity on YouTube, Apple Podcasts, Overcast, Spotify and all the casts. You also can follow Equity on X and Threads, at @EquityPod. 

When Lydia Peabody saw her friend pull out a flip phone at a party last year, she burst out laughing.

“I was like, ‘Girl, what are you doing with that thing? That has to be a joke!’” Peabody told TechCrunch. But it wasn’t just a prop — her friend was participating in Month Offline, a community challenge in which a small cohort of people exchange their smartphones for flip phones.

Peabody couldn’t fathom giving up her smartphone, but her friend inspired her. A year later, her life looks different. She left her career as a licensed therapist to become the founding CMO of Dumb Co, the flip phone company that grew out of Month Offline. She’s happier.

“I did Month Offline, and I was like, ‘Whoa, why am I suddenly not anxious? Am I feeling good?’” she said. “I didn’t even know that this is what I needed, and that spending this much time on my screen after work was causing me to feel so yucky.”

Dumb Co sells flip phones that sync to your smartphone, rather than replace it, forging a happy medium between the infinite connectivity of the iPhone and the unrealistic limitations of an early 2000s relic. Funded by friends and family, the company is run by a small team in their 20s and early 30s. Like their peers, they’re dissatisfied with the fast pace of plugged-in, frictionless life. They grew up with iPads and Instagram but now crave something simpler.

In the humble shell of a $20 TCL flip phone, Dumb Co loads its own software so that users can access apps like WhatsApp, Spotify, Apple Music, and Uber. You can even access iMessage through a third-party app (shh, don’t tell Apple). By packaging familiar comforts like music streaming, maps, and blue bubble texts in a flip phone, Dumb Co is creating something for people who want to reduce their screen time and be more present but struggle to fully disconnect in a world built for the smartphone.

“We are trying to make something where you can leave your smartphone at home and literally just live your life and engage with other people,” Afreka Ebanks, Dumb Co’s communications director, told TechCrunch. “And when you want to be on your smartphone and you come back home, you can use it, because the feature for call forwarding and text forwarding can be turned off.”

I spent over a month testing the device — which Dumb Co calls the Dumb Phone — buoyed by the knowledge that in case of emergency, I always had my iPhone on hand. I didn’t use the Dumb Phone that much at first, but as I carried it around to show my friends, I noticed that they weren’t confused by my flip phone — they were envious of it.

“I’ve been getting into a lot of interesting conversations with people as I’m walking and someone sees me at the stoplight like, ‘What is this thing you have?’” said Ebanks, who bedazzled her flip phone. “I think it’s a great conversation starter, and I think it’s incredible watching people — myself included — work through the awkwardness of socializing with others, because I’m no longer distracted because I’m looking down at my phone.”

The Dumb Phone is clunky at times. It’s slower than I’m used to, and I end up spending more time typing T9 texts than if I just used my iPhone (what I really want is a dumb Sidekick with a QWERTY keyboard). Yet there’s something undeniably refreshing about knowing that if you want to open social media, take a picture you’ll never look at again, or check your email, you can’t.

When I talked to Peabody toward the end of my month of dual iPhone/flip phone ownership, she asked if I had ever left the house with just my flip phone. I confessed that I had not. I explained that sometimes I need to check public transit schedules, or keep up with Slack if I go to an appointment during the day.

“The truth is, when you say the word need, it almost gives the same meaning as like, ‘I need food or shelter,’” Peabody told me. “Yeah, sure, it’s actually helpful to know when the buses are coming, but if you don’t have that information, you turn to your neighbor and say, ‘Do you know when the next bus is coming?’”

Peabody dared me to leave my iPhone at home. The day we spoke, I had already planned to report on an event at a library across town. I tried to explain that I had never been to this library and wasn’t sure what subway stop to get off at. She told me to just write down directions before I left. I worried that I wouldn’t be able to record interviews at the event. She told me that the Dumb Phone can record audio.

“I really, really want you to do this, because I know that this is something that’s best experienced,” Peabody said. “When I switched to a Dumb Phone last summer, I did not use my smartphone for seven weeks, and I went on a cross-country road trip to New Mexico. I did not think I could do that, but I’m telling you that you can.”

I was running out of excuses. Peabody drove thousands of miles without a smartphone. How could I tell her that I needed my iPhone so that I could triple-check that Tasker-Morris is the right train stop?

Smartphones and social media are not a one-sided evil. There’s real value in connecting with friends online, sending pictures of your dog to your grandma, and using Apple Pay when you forget your wallet. While researchers don’t classify smartphone dependence like they would a substance addiction, there are certainly parallels. Not everyone has an adversarial relationship with their phone, but for people like me, more screen time often makes me feel more anxious, unfocused, and less grounded. Peabody even compared her relationship with her phone to getting hooked on Juul in college.

“It was really, really hard, but I totally broke that addiction, and now when I see a vape or something, I actually detest it — I’m like, ‘Oh no, I do not want that,’” she said. “When I turned off my smartphone for seven weeks, I would think about using it again, and I felt that same repulsion. I actually didn’t look at it or touch it.”

I was nervous to leave my iPhone at home, but I trusted my knowledge of the transit system and managed to get myself across town without my iPhone (I will admit, I texted someone just to be extra super sure that the library is off the Tasker-Morris stop). When I needed to send a text that was too long for T9 typing, I sent a voice message. I felt more connected with the world around me, and nothing went wrong.

I don’t see myself exclusively switching to the Dumb Phone, but I find it valuable as a tool to help me pay more attention to how and when I’m using my smartphone. The Dumb Phone ships with a black velour pouch, which you’re supposed to put your smartphone in when you leave it at home. I can’t quit the iPhone cold turkey, but I tossed the velour pouch in my bag on a beach trip, just in case. I used it for a few things, like ordering food and checking train times. But while I enjoyed a day on the beach, I didn’t take out my phone. I had a book, a sandwich, two bottles of water, some sunscreen — what else could I need?