Reed Jobs focuses on curing cancer, not his famous name

Reed Jobs is disarmingly easy to talk to. He speaks at a rapid clip, cracks jokes about his own tech preferences, and lights up when the conversation shifts away from his last name and toward his real passion: cancer research. When a producer asked if he was using a MacBook for our video call, his response was immediate and wry: “Are you kidding?”

What truly energizes him is Yosemite, the oncology-focused venture firm he founded in 2023. The model is distinctive: blend philanthropy with venture capital to build biotech companies from the ground up, starting with early academic research. Three years in, Jobs sees the window of opportunity widening faster than he anticipated, driven by the collision of artificial intelligence with drug discovery and clinical trial design.

Among Yosemite’s standout portfolio companies are Azalea, born from a grant to Nobel laureate Jennifer Doudna’s lab and now in clinical trials, and Quarry, built with serial founder Craig Crews around induced proximity , a novel approach where a drug physically drags a disease-causing protein next to the cell’s own breakdown system, rather than trying to block it directly.

When we last spoke with Jobs at TechCrunch Disrupt nearly three years ago, Yosemite was brand new and biotech was still recovering from its post-pandemic crash. Today, the firm employs 17 people, a cluster of blockbuster drugs are losing patent protection simultaneously, and AI has become central to Yosemite’s operations. We sat down to get an update.

This interview has been edited for length and clarity.

TechCrunch: You announced the first close of your second fund earlier this year, targeting $350 million. What’s the state of Yosemite right now?

Reed Jobs: We’re in a period of extreme activity. We’ve seen incredible traction and brought on many important new partners. Yosemite is unique for two reasons: we focus exclusively on oncology , that’s 40% of all biotech , and we prefer to create our own companies. We don’t believe the cures for cancer are sitting on pharma shelves waiting to be found. We think we need to go make them using new knowledge. To de-risk those ideas early, when they’re still fragile concepts in university labs, we use a small amount of philanthropy with no strings attached. Out of our first fund’s 20 companies, two came directly from grants.

How much of that $350 million goes into companies you’re building yourselves versus ones you’re joining?

About a third goes into companies we create , either our own ideas or ones we develop alongside academics at places like Yale, Berkeley, and Stanford. That takes enormous time and energy, which is why it’s only a third. The rest goes into companies others have built that we want to join. Separately, 2.5% of the fund’s assets under management goes into a donor-advised fund , pure grant money with no strings, plus $1 million a year from our management fees.

It’s early, but what’s your pitch to limited partners on performance versus other life science VC firms?

It’s very early for us, but Yosemite has the ability to create new areas of medicine before other firms get there. My team has pioneered epigenetic gene editing , technology that changes how strongly a gene is expressed without altering the DNA sequence itself , and safe delivery of gene editing to specific cells, a bottleneck for the entire field for nearly a decade. If you want to be first and help discover new areas, that’s what we’ll be best at.

You were worried earlier about how conservative biotech investors had become. Has that changed?

It has, actually. When I launched Yosemite in 2023, the XBI was still down massively from its 2021 highs, and pharma hadn’t started buying 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 has led to an acquisition spree over the last eight months. We’ve seen huge exits , Eli Lilly buying Kelonia for $7 billion , and massive wins in antibody drug conjugates. One high-profile example: Revolution Medicines, targeting KRAS in pancreatic cancer, has doubled survival rates for the most common form of pancreatic cancer, from 12 to 24 months. That happened just in the last year.

Last year you expressed concerns about 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 40% cut to the NIH budget. For context, the biggest cut ever was 1% in 2009, during the global financial crisis, and that cost 7,000 NIH scientists their jobs. Gratefully, the Senate and House , in a bipartisan move , totally rejected the 40% cut. This year they came back asking for 12%, still the biggest cut ever 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 machines and floppy disks. 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, and 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 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 pocket for a drug molecule to latch onto , 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 , a noninvasive therapy that creates small air pockets, then collapses 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.