Reed Jobs comes across as likable and engaging, known for his rapid speech, humor, and passion for his work. While he prefers not to dwell on being Steve Jobs’s son, he handles the topic with ease. When asked by our producer, Maggie, if he was using a MacBook during our video call on Thursday morning, he swiftly responded, “Are you kidding?”
His primary focus is on Yosemite, an oncology-centered venture firm he started in 2023. The firm aims to create biotech companies from the ground up, leveraging early academic research and combining philanthropy with external investment. Three years in, Jobs is determined to position Yosemite as a substantial force, driven by the accelerating opportunities AI presents in drug discovery and clinical trial design.
Among the companies under Yosemite’s portfolio that he is most proud of are Azalea, which originated from a grant to Jennifer Doudna’s lab and is now in clinical stages, and Quarry, developed with serial entrepreneur Craig Crews, utilizing a unique therapeutic method called induced proximity. This method involves a drug that brings a disease-causing protein close to the cell’s breakdown system rather than directly blocking it.
Reflecting on our last meeting with Jobs at JS Disrupt almost three years ago, Yosemite was in its infancy, and the biotech sector was still recovering from a post-pandemic slump. Now, with a team of 17, the firm is poised to exploit new opportunities as several major drugs face patent expiration, and AI has become integral to Yosemite’s operations, according to Jobs.
This Q&A has been edited for brevity.
TC: Earlier this year, you announced the initial closing of your second fund, aiming for $350 million. How is Yosemite currently faring?
RJ: We are experiencing a period of intense activity. We’ve seen remarkable progress and have welcomed several significant new partners. Yosemite is distinct in two ways: we exclusively focus on oncology—comprising 40% of biotech—and we prefer to develop our own companies. We believe that the cures for cancer aren’t simply waiting in the pharmaceutical industry; we must create them using new insights. We mitigate risks early by supporting fragile ideas in university labs with philanthropy, wholly without strings attached. Two of our 20 initial fund companies stemmed directly from a grant.
How is the $350 million allocation divided between companies you’re creating and those you’re joining?
About one-third is dedicated to companies we create ourselves—either from our own ideas or in collaboration with academics at institutions like Yale, Berkeley, and Stanford. This requires substantial time and effort, hence the one-third allocation. The remainder supports existing companies we wish to partner with. Additionally, 2.5% of the fund’s assets under management go into a donor-advised fund, offering no-strings-attached grant money, plus $1 million annually from our management fees.
It’s early, but how do you convince potential LPs of your performance compared to other life science VC firms?
Though we’re in early stages, Yosemite is positioned to pioneer new medical fields before others. Our team has led advancements in areas like epigenetic gene editing and precise delivery of gene editing to specific cells, which have been challenging for the field for nearly a decade. If you want to be a front-runner in discovering new areas, we’re your best bet.
Previously, you expressed concern about conservative biotech investors. Has that situation evolved?
Yes, it has. When I launched Yosemite in 2023, the XBI index was still significantly down from its 2021 peak, and pharma wasn’t in acquisition mode. In the past three years, interest rates have improved, and pharma is facing its largest patent cliff in history with substantial cash reserves from the pandemic. This has led to an acquisition spree over the last eight months. We’ve witnessed significant exits, like Eli Lilly acquiring Kelonia for $7 billion, and notable successes in antibody drug conjugates. For example, Revolution Medicines, targeting KRAS in pancreatic cancer, has doubled the survival rate for the most common form of the disease—from 12 to 24 months—just in the past year.
Last year, you voiced concerns about proposed NIH budget cuts. What’s the current status?
The pressure from the federal government remains, though it’s less of a long-term threat than before. Last year, for the first time, an administration proposed a 40% NIH budget cut. Historically, the largest cut was 1% in 2009, costing 7,000 NIH scientists their jobs. Fortunately, the Senate and House—strongly bipartisan—rejected the 40% cut. This year, they proposed a 12% cut, still historically large, but I anticipate the same rejection. NIH funding enjoys over 90% approval. Personally, I believe we should be proactive—increasing it to around $100 billion. In dollar terms, it hasn’t grown in a decade, effectively shrinking relative to inflation.
Where is AI already transforming healthcare delivery?
American hospitals are technologically outdated—still relying heavily on fax and floppy disks. For instance, call centers like 911 triage are costly to run around the clock and are prime candidates for AI integration. AI can also revolutionize electronic health records, radiology, and pathology. However, I find clinical trials most promising—these are the biggest expenses and time sinks in drug development. A Phase 3 cancer trial costs about $260 million, with only one in three succeeding. The largest expense is patient recruitment and retention. AI could create a synthetic control arm, reducing the need for a full control group and significantly speeding up the process. The FDA is currently exploring this.
Is AI in drug discovery overhyped?
AI represents a remarkable leap forward, democratizing science and accelerating processes. Currently, AI is expediting much of the tedious work—not necessarily improving it, but doing it at incredible speed with consistent results.
AI has also excelled at identifying previously unreachable pockets. Historically, we could only target about 15% of the genome because protein-protein interactions were too complex. This has changed recently, thanks to AI. Revolution Medicines is pioneering this by targeting KRAS, which was long deemed untargetable due to its smooth, oval shape, akin to a ‘death star.’ About a decade ago, Amgen scientists discovered a hidden pocket, leading to the first drug against it, Lumakras. It was effective for one mutation; AI has since identified other mutations that can now be targeted and devised innovative ways to block them.
Which hard-to-target areas are your companies focusing on?
The most significant target is p53. We’re addressing it with three companies using multiple strategies. It’s a tumor suppressor gene—elephants, known for their cancer resistance, have numerous p53 copies, whereas humans have one, which can be easily compromised. p53 is frequently suppressed in human cancers; nearly every cancer requires its deactivation to develop. If we could reactivate it or combat its mutated forms, it could be a game-changer in cancer treatment, an opportunity we’ve yet to seize. We believe we’ve identified an approach to target the exposed marker across various p53 mutations.
Can you tell me about Tune Therapeutics?
Tune is the leading epigenetic editing company in clinical development, focusing on hepatitis B, which affects over 250 million individuals and is a primary liver cancer cause. The technology allows us to add or remove methyl groups, small chemical tags that modify a gene’s activity level without altering the gene itself, at specific liver sites. All cells in your body share the same DNA but express it differently—consider gray hair, where melanin is methylated and turned off, resulting in less robust hair production. This process is also behind aging immune systems and slowing metabolism. Hepatitis B appears foreign to the body, and we’re working to methylate and silence the virus itself, similar to the natural clearance observed in around 1% of individuals.
Histosonics is a device company, which is atypical for Yosemite. Why the interest?
You’re correct; we typically don’t invest in devices. Histosonics is pioneering large-scale histotripsy for noninvasive liver tumor destruction. This method uses small air pockets, collapsing them to destroy tissue in a precise area, akin to ultrasound rather than a CT scan. Their primary focus is on pancreatic and liver tumors—most pancreatic cancers metastasize to the liver, making it a logical combination. We believe this will become a significant part of therapy for both conditions.
How many companies are currently in your portfolio, and have there been any setbacks?
We have close to 25 companies across both funds. Two have not succeeded for scientific reasons. We allocate investments based on scientific milestones, and given our early-stage focus, scientific failures are expected.
What advice do you offer founders contemplating a substantial offer from major pharmaceutical companies? Accepting such an offer can limit other options.
Pharmaceutical companies are essential partners, but founders must view them as dynamic entities—their priorities can shift based on leadership. Post-COVID, many pharma companies incurred losses in infectious disease areas and exited the space entirely—take Pfizer, for example. It’s crucial to stay informed on which companies are actively pursuing your area of interest.
How can founders interested in connecting with you do so?
Our approach is open and inclusive. When evaluating grants and companies, we remove personal identifiers like CVs—I prefer not to know who owns an idea or what title someone holds. We’ve funded both Nobel laureate labs and first-time grant recipients, and I’m equally pleased with either result. We explore all modalities, including small molecules, radiopharmaceuticals, gene therapy, immunotherapy, AI, and digital health. Please email us. We’re eager to hear about any idea that can impact cancer patients.
Does storytelling hold as much weight for biotech founders as in other sectors?
Unfortunately, yes—I’ve witnessed companies with promising science falter due to poor storytelling by the CEO. Typically, the founder and CEO are distinct roles. The founder is often the academic, serving as the chief scientist or medical officer, while the CEO is a professional operator responsible for raising capital and narrating the company’s story. This division of labor is effective.
Looking back on three years of leading Yosemite, what has surprised you the most?
We’ve reached a milestone with Eli Lilly becoming the first trillion-dollar pharmaceutical company, driven by GLP-1s—the world’s top-selling drug class. Early indications suggest GLP-1s may protect against neurodegenerative diseases and cancer, beyond weight loss benefits. Obesity is one of only two “pan-disease” risk factors—the other being smoking—that elevate risks across nearly every disease category. This has prompted renewed interest, ambition, and investment in vast disease areas that had stagnated. Genes like KRAS, Myc, beta-catenin, and p53—the elusive pantheon of oncogenes—are now within reach, in our view. I didn’t anticipate Yosemite would progress so swiftly. This moment is more significant than I realized, which is both intimidating and empowering.
Before we conclude, what are your thoughts on the longevity industry?
I have no desire to die soon, and longevity is personally important. However, I don’t think we—or anyone—truly understand the field yet. Consult a geneticist, and they’ll discuss telomeres; an immunologist will focus on T cells losing efficacy, while a metabolomicist may offer a different perspective. There’s no unified theory of aging akin to physics. I don’t believe there’s a singular “longevity problem”—our bodies age differently across cell types, and the interplay of these factors constitutes aging. Healthcare should aim to optimize this on an individual basis, but I’m unsure how longevity can be turned into a universal business model.
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