Reed Jobs, founder of the oncology-focused venture firm Yosemite, doesn’t want to talk about his last name. He’d rather discuss Yosemite, the firm he launched in 2023 that uses a hybrid model of philanthropy and venture capital to build biotech companies from early academic research. In a wide-ranging interview, Jobs detailed how the collision of AI with drug discovery and clinical trial design is expanding opportunities faster than he expected, and outlined his firm’s aggressive pursuit of historically undruggable cancer targets.
Yosemite’s unique model: Philanthropy meets venture capital
Yosemite, which Jobs describes as operating exclusively in oncology — roughly 40% of all biotech — has a team of 17 and has raised a second fund targeting $350 million. The firm’s approach is distinctive: it uses a donor-advised fund, funded by 2.5% of assets under management plus $1 million annually from management fees, to provide no-strings-attached grants to university labs. This de-risks early ideas before they become venture investments. Two of the 20 companies in Yosemite’s first fund originated directly from such grants, including Azalea, born from a grant to Nobel laureate Jennifer Doudna’s lab and now in clinical trials.
Also read: NHTSA gives robotaxi developers ultimatum on first responder interference
About a third of the new fund will go into companies Yosemite builds itself, often alongside academics at institutions like Yale, Berkeley, and Stanford. The remainder will go into companies founded by others that the firm wants to join. Jobs emphasizes that the model allows Yosemite to create new areas of medicine before other firms get there, citing early work in epigenetic gene editing and safe delivery of gene editing to specific cells.
AI’s accelerating role in drug discovery
Jobs is bullish on AI’s impact, calling it a “fantastic advancement” for democratizing science and accelerating the grunt work of drug discovery. He notes that AI has been instrumental in finding new drug targets, particularly in areas that were previously considered undruggable. Historically, only about 15% of the genome could be targeted with drugs because the chemistry of protein-protein interactions was too difficult. That has changed in the last few years, hand in hand with AI.
A prime example is the KRAS gene, a common driver of pancreatic and other cancers. For decades, KRAS was considered undruggable because its surface is a smooth oval with no natural pocket for a drug to latch onto. In 2021, Amgen’s Lumakras became the first approved drug targeting one specific KRAS mutation. Jobs says AI has now enabled researchers to find other variants and creative new ways to block the protein, with Revolution Medicines recently doubling the survival rate for the most common form of pancreatic cancer from 12 to 24 months.
Targeting the pantheon of undruggable oncogenes
Yosemite is going after the biggest prize of all: p53, the most frequently mutated gene in human cancer. “Almost every cancer has to knock it out to exist in the first place,” Jobs said. He revealed that Yosemite is attacking p53 with three different companies and multiple strategies, including targeting a newly discovered marker on the mutated protein. Other targets include Myc and beta-catenin, part of what Jobs calls the “pantheon of oncogenes that have evaded us for decades.”
The firm’s portfolio also includes Tune Therapeutics, a leader in epigenetic editing targeting hepatitis B, which is the primary driver of liver cancer, and Histosonics, a device company using noninvasive ultrasound technology called histotripsy to destroy liver tumors.
The patent cliff and a changing biotech environment
Jobs notes that the investment environment has improved significantly since Yosemite’s launch in 2023, when biotech was still reeling from the post-pandemic crash. A cluster of blockbuster drugs losing patent protection in the same window, combined with record cash reserves at pharmaceutical companies, has triggered an acquisition spree. Eli Lilly’s $7 billion purchase of Kelonia is one high-profile example. Jobs also pointed to the success of GLP-1 drugs like Ozempic, which has created the first trillion-dollar pharmaceutical company and is driving renewed interest in large disease areas that had gone cold.
Despite ongoing pressure from the federal government on NIH funding, Jobs is optimistic, noting that bipartisan support in Congress has rejected proposed cuts. He argues that NIH funding has not grown in dollar terms for a decade and should be increased to $100 billion annually.
Advice for founders and the future of longevity
Jobs advises founders to be cautious about taking large checks from big pharma, as priorities can shift with leadership changes. He also emphasizes that Yosemite has an open door for founders, saying the firm removes CVs from the grant review process and is equally happy funding Nobel laureates and first-time applicants. On the longevity industry, Jobs is skeptical of a one-size-fits-all approach, arguing that aging is a complex interaction of different cell types and that there is no grand unified theory yet.
“This time is more important than I realized,” Jobs said. “Which is both scarier and more empowering.”
Frequently Asked Questions
What is Yosemite’s investment strategy?
Yosemite focuses exclusively on oncology, using a combination of no-strings-attached philanthropy to de-risk early academic ideas and traditional venture capital to build and invest in biotech companies.
How is AI being used in Yosemite’s portfolio?
AI is accelerating ‘grunt work’ in drug discovery, helping to find new drug targets like KRAS, and is being explored for use in clinical trial design, such as creating synthetic control arms to reduce patient recruitment costs.
What are the most challenging cancer targets Yosemite is pursuing?
The firm is going after p53, the most frequently suppressed gene in human cancer, which has never been successfully targeted, and is also involved in epigenetic gene editing and safe delivery of gene therapies.
How has the biotech funding environment changed since 2023?
Lower interest rates and a major patent cliff facing pharmaceutical companies have led to an acquisitive spree, with large exits like Eli Lilly’s $7 billion purchase of Kelonia, improving the exit environment for venture-backed biotech.
