Yosemite venture firm closes first close of second fund, eyes AI-driven oncology breakthroughs
Yosemite venture firm secures first close of a $350M-target fund, using AI and philanthropy to build oncology startups and pursue undruggable targets.
Reed Jobs’s oncology-focused venture firm Yosemite announced a milestone first close of its second fund as it doubles down on building biotechs from early academic research. The firm, founded in 2023, is targeting $350 million and says about one-third of the capital will seed companies it spins up directly while the remainder will back external teams and follow-on investments. Yosemite is also formalizing a donor-advised grant pool to de-risk early science, and its leaders highlight AI and recent pharma acquisitiveness as catalysts for faster progress.
Fundraising and strategy update
Yosemite completed a first close earlier this year as it seeks to expand a portfolio now approaching 25 companies across two funds. The firm’s model combines traditional venture capital with no-strings philanthropic grants to accelerate early-stage discovery at universities. Management estimates roughly one-third of fund commitments will finance companies Yosemite creates or co-creates, with the balance reserved for investments in outside-founded startups.
Portfolio advances and clinical momentum
Several portfolio companies have moved into the clinic, underscoring the firm’s emphasis on translational science. Azalea, originating from a grant to a prominent genome-editing lab, and Quarry, which pursues an induced-proximity therapeutic approach, are cited as early successes now advancing clinical programs. Yosemite reports it tranches investment against scientific milestones, accepting that a small number of projects will fail for scientific reasons as part of an expected attrition curve.
AI’s role in discovery and trials
Reed Jobs describes AI as central to Yosemite’s evolving playbook, speeding up both discovery and clinical development tasks. AI tools are helping to identify previously hidden druggable pockets and to prioritize targets across complex proteins, widening the range of molecules scientists can pursue. Jobs also highlights the potential for synthetic control arms and AI-enabled patient matching to shrink trial sizes and cut the time and cost of Phase 3 studies, which he notes remain the most expensive step in oncology development.
Targeting historically undruggable genes
A core objective for Yosemite is pursuing targets that have resisted traditional approaches, with a particular focus on the tumor suppressor p53. The firm says multiple portfolio companies are pursuing different strategies to restore or exploit p53 function across diverse cancer types. Yosemite also points to interest in oncogenes long considered out of reach, arguing that recent advances in chemistry, biology and AI now make genes such as KRAS and MYC more tractable.
Philanthropy, partnerships and exits
Yosemite’s hybrid model includes a donor-advised fund receiving a portion of management fees and additional philanthropic capital to underwrite high-risk, early science. That approach aims to lower entry barriers for nascent ideas emerging from academic labs, regardless of the principal investigator’s track record. Meanwhile, a buoyant market environment and a wave of patent expirations are prompting heightened pharma acquisition activity, which Yosemite sees as creating exit opportunities for successful assets.
Advice to founders and industry outlook
The firm stresses a pragmatic view toward pharma partnerships, warning founders that big-company priorities can shift with leadership changes and that taking a large upfront check can close other strategic paths. Yosemite maintains an open intake for ideas across modalities, from small molecules and gene therapy to digital health and devices, and says it evaluates science independent of pedigree. Looking ahead, the firm believes the convergence of AI, fresh capital flows and a deeper pipeline of druggable biology sets up a faster era for oncology innovation.
Yosemite says it intends to keep building from first principles: translating early academic discoveries into companies with the scientific rigor and operational discipline to advance toward the clinic. The firm frames its work as patient-focused and high-risk by design, aiming to move rapidly on ambitious targets while accepting the normal failure rate of early-stage science.
