Reed Jobs would rather talk about curing cancer than his last name

Yosemite, the oncology-focused venture capital firm founded by Reed Jobs, is expanding its investment reach by combining philanthropic grants with traditional venture capital to accelerate cancer research. The firm, which recently sought to close its second fund at $350 million, leverages artificial intelligence to streamline drug discovery and clinical trial design, aiming to address critical bottlenecks in biotechnology, according to interviews with Jobs.

Yosemite’s Investment Strategy in Oncology

Yosemite operates with a distinct model within the life sciences sector, focusing exclusively on oncology, which accounts for approximately 40% of the broader biotech market. The firm utilizes a hybrid funding approach: roughly one-third of its capital is deployed into companies built internally or in collaboration with academic institutions like Yale, Stanford, and Berkeley. The remaining two-thirds are directed toward external investments in existing startups.

A core component of the firm’s structure is its commitment to philanthropy. According to Jobs, 2.5% of the firm’s assets under management are allocated to a donor-advised fund, supplemented by $1 million annually from management fees. This capital provides "no-strings-attached" grants to university labs, allowing the firm to de-risk early-stage research before formal venture investment.

AI Integration in Drug Development

The firm is increasingly utilizing artificial intelligence to resolve inefficiencies in clinical trials and target identification. Yosemite identifies patient recruitment and retention as the primary cost and time sinks in Phase 3 cancer trials. By implementing synthetic control arms—computer-generated comparison groups derived from existing patient data—firms can potentially reduce the number of human participants required, thereby accelerating trial timelines.

AI is also being used to identify "druggable" pockets on proteins that were previously considered inaccessible. A notable example in the firm’s portfolio is Revolution Medicines, which is targeting KRAS mutations. Historically, these mutations were viewed as nearly impossible to treat due to the protein’s smooth surface; however, recent advancements in computational chemistry have enabled the development of therapies to block these oncogenes.

Targeting Previously Undruggable Proteins

Yosemite is currently pursuing therapies for p53, a tumor suppressor gene frequently suppressed in human cancers. The firm is backing three separate companies employing different strategies to either reactivate p53 or target its mutated forms.

Other notable portfolio companies include:

• Tune Therapeutics: Focused on epigenetic editing to silence viruses, such as the hepatitis B virus, which is a primary driver of liver cancer.
• Histosonics: A device company utilizing histotripsy, a non-invasive ultrasound-based therapy, to physically destroy tumors in the liver and pancreas.
• Azalea: Developed from research in Jennifer Doudna’s lab, this company is currently testing new therapeutic approaches in clinical settings.

Market Context and Future Outlook

The biotech investment landscape has shifted significantly since 2023. According to Jobs, the industry is currently benefiting from an acquisitive environment driven by a "patent cliff," where major pharmaceutical companies face the expiration of blockbuster drug patents and are seeking to replenish their pipelines using record cash reserves.

While previous budget proposals suggested significant cuts to NIH funding, these have faced bipartisan opposition in Congress. Jobs argues that funding should ideally increase to $100 billion to account for inflation and to sustain the pace of oncology research.

Key Takeaways

• Portfolio Growth: Yosemite has grown to a team of 17 and maintains a portfolio of nearly 25 companies across two funds.
• Scientific Milestones: The firm utilizes a tranches-based investment strategy, often withdrawing from projects that fail to meet specific scientific milestones in their early stages.
• Industry Trends: The rise of GLP-1 receptor agonists has shifted focus toward the intersection of metabolic health and chronic diseases, including cancer and neurodegeneration, prompting renewed interest in "pan-disease" risk factors.
• Founding Philosophy: Yosemite emphasizes a division of labor where academics serve as founders and chief scientists, while professional operators act as CEOs to manage capital and corporate strategy.