Reed Jobs is personable, quick‑spoken, self‑deprecating and fond of video‑game analogies. He does not shy away from being Steve Jobs’s son, but prefers to focus on Yosemite, the oncology‑only venture firm and operator he launched in 2023. Yosemite’s explicit mission is to build biotech companies from early academic research using a blend of philanthropy and outside investment capital.
Three years after founding the firm, Jobs says Yosemite is positioning itself as a serious player. He credits accelerating opportunities to AI’s impact on drug discovery and clinical trial design. He highlighted portfolio companies such as Azalea — spun out of a grant to Jennifer Doudna’s lab and now in the clinic — and Quarry, which was built with serial founder Craig Crews around an induced‑proximity therapeutic approach.
Fund strategy and allocation
Yosemite announced the first close of its second fund earlier in the year, targeting $350 million. Jobs explained that roughly one third of that capital goes into companies Yosemite is creating itself, either from internal ideas or in partnership with academics at institutions such as Yale, Berkeley and Stanford. The remainder is allocated to companies started by others that Yosemite joins. Additionally, 2.5% of the fund’s assets under management are placed in a donor‑advised fund for no‑strings‑attached grants, and the firm directs $1 million per year from management fees into that grant pool.
Because Yosemite operates very early on science that is still nascent in university labs, investments are often tranch‑based against scientific milestones. That approach has led to two exits so far that were closed for scientific reasons — an expected outcome when working at such an early stage.
Performance case and market context
Jobs argues Yosemite’s edge is the ability to create new areas of medicine before other firms arrive. He cites the team’s role in pioneering epigenetic gene editing and safer cell‑specific delivery of gene editors — areas that were bottlenecks for years.
The broader biotech market has shifted since Yosemite’s 2023 launch. Interest rates have improved and pharmaceutical companies face a historic patent cliff while holding large cash reserves from the pandemic period. That combination has driven acquisitive activity over the past several months. Jobs pointed to big exits such as Eli Lilly’s purchase of Kelonia for $7 billion and to clinical advances like Revolution Medicines’ work on KRAS, which has doubled median survival in the most common form of pancreatic cancer from 12 to 24 months in the last year.
On NIH funding, Jobs recalled last year’s proposal from an administration to cut up to 40% of the NIH budget — a measure the Senate and House ultimately rejected. He noted that this year a 12% cut was again proposed and that NIH funding historically has very strong bipartisan support. Jobs personally would like to see NIH funding increased substantially; he said it has not grown on a dollar basis for roughly a decade and has effectively shrunk relative to inflation.
Where AI is changing healthcare
Jobs described U.S. hospitals as technologically behind in many administrative areas and highlighted use cases for AI in call centers, electronic health records, radiology and pathology. His strongest interest, however, is clinical trials: a Phase 3 cancer trial costs roughly $260 million and only about one in three succeed. Patient recruitment and retention are the biggest drivers of cost and time. AI can enable synthetic control arms — computer‑generated comparators built from existing patient data — so trials might only need to recruit the active treatment arm, halving required patient numbers and greatly speeding trials. Jobs said the FDA is increasingly open to these ideas.
On drug discovery, Jobs described AI as an accelerant for much of the “grunt work,” enabling reproducible and rapid progress. He also credited AI with helping find pockets on proteins that historically were considered undruggable — for example, the recent progress against KRAS where researchers discovered cryptic pockets that allow drugs to bind.
Targeting historically undruggable genes
One of Yosemite’s largest bets is on p53, the tumor suppressor gene. Jobs said the firm is pursuing p53 across three different companies and several strategies. Because p53 function is commonly lost in human cancers, restoring or targeting its mutated forms could be a widespread therapeutic vulnerability. Jobs said they believe they have identified an exposed marker that appears across different mutational mechanisms affecting p53.
Notable portfolio companies
- Azalea: originated from a grant to Jennifer Doudna’s lab and now in the clinic.
- Quarry: developed with Craig Crews, uses induced‑proximity approaches to degrade disease‑causing proteins by recruiting them to the cell’s degradation machinery.
- Tune Therapeutics: a leader in clinical‑stage epigenetic editing, targeting hepatitis B — a virus that affects more than 250 million people worldwide and is a leading cause of liver cancer. Tune’s technology modulates DNA methylation at specific sites in the liver to silence viral activity.
- Histosonics: an outlier for Yosemite because it is a device company. It uses histotripsy, a noninvasive therapy that creates and collapses microbubbles to destroy tissue in targeted regions; lead programs are focused on pancreatic and liver tumors.
Portfolio size, failures and advice to founders
Across both funds, Yosemite’s portfolio is close to 25 companies and the firm’s team has grown to 17 people. Two investments have been closed for scientific reasons. Jobs counsels founders who receive large checks from pharma to consider that such deals can restrict future options, and that pharma priorities shift with leadership; staying aware of who is active in a therapeutic area is critical.
Yosemite says it has an open door for pitches and evaluates ideas without regard to CVs or titles: they have funded Nobel laureate labs and first‑time grant recipients alike. They review every modality — small molecules, radiopharmaceuticals, gene therapy, immunotherapy, AI and digital health — and invite submissions for anything that could affect cancer patients.
Storytelling, surprises and longevity
Jobs acknowledged that storytelling matters in biotech because CEOs must raise capital and articulate a credible plan; founders (often academics) and CEOs frequently play distinct roles, which he finds effective.
One of Yosemite’s biggest surprises in three years has been the speed of change in the industry, partly driven by GLP‑1 drug sales and wider interest in areas previously considered intractable. Jobs said he did not expect the firm to move so quickly and described the current moment as both daunting and empowering.
On the longevity industry, Jobs is personally interested but cautious: he said there is no single unified theory of aging accepted across disciplines. Different experts emphasize telomeres, immune function, metabolism or other mechanisms. Jobs believes aging varies across cell types and that optimizing those differences is a personalized healthcare problem rather than a one‑size‑fits‑all business.
Conclusion
Yosemite has spent three years building a focused oncology venture operation that mixes early philanthropic grants with venture capital to create companies from academic discovery. With a 17‑person team, nearly 25 companies in the portfolio, a second fund targeting $350 million, and growing AI capabilities, the firm is attempting to tackle historically difficult targets such as p53 while adapting to rapid market and technological change.
