The Yosemite oncology fund is moving faster than its founder expected. Reed Jobs, speaking in a wide-ranging interview, says the firm has grown to 17 people, is closing in on 25 portfolio companies across two funds, and has watched a once-cautious biotech market turn acquisitive almost overnight.
The catalyst is straightforward, if long in coming: a pharmaceutical patent cliff of historic scale, record cash reserves built up during the pandemic, and falling interest rates. Deals like Kirkland-advised Eli Lilly’s acquisition of Kelonia Therapeutics illustrate what that looks like in practice. The headline figure is $7 billion; $3.25 billion of that is paid upfront, with the remainder contingent on clinical, regulatory, and commercial milestones, and the transaction is expected to close in the second half of 2026. Goodwin, which advised Kelonia, describes the deal as the largest in vivo CAR-T transaction to date. Kelonia’s lead programme, KLN-1010, is an investigational one-time intravenous gene therapy targeting BCMA, a protein expressed on multiple myeloma cells, and is currently in Phase 1 development (the inMMyCAR study).
Jobs flags it as exactly the kind of exit that changes LP conversations. Yosemite’s second fund is targeting $350 million. About a third of that goes into companies the firm builds itself, often alongside academics at Yale, Berkeley, and Stanford, with 2.5% of assets channelled into a donor-advised fund for no-strings-attached grant money, topped up by $1 million a year from management fees.
Revolution Medicines and the Yosemite Oncology Fund’s KRAS Thesis
Jobs points to Revolution Medicines’ work on KRAS, long described as undruggable, as evidence that the field’s ambitions are finally matching its science. Revolution’s drug daraxonrasib produced headline Phase 3 results that CNBC reported as slashing the risk of death by 60% versus chemotherapy, in a cancer with a five-year survival rate of just 13% and no prior drug showing an overall survival benefit of more than one year in a Phase 3 setting.
The survival numbers carry a nuance worth flagging. Jobs describes the result as doubling median survival from 12 to 24 months. BioPharma Dive’s ASCO data report median overall survival of 13.2 months for daraxonrasib recipients versus 6.6 months for chemotherapy patients with RAS G12 mutations. The characterisations reflect different cuts of the data; the 60% reduction in death risk is the pre-specified primary endpoint result. Either way, the direction is unambiguous.
The FDA awarded daraxonrasib Breakthrough Therapy designation for previously treated metastatic pancreatic cancer with KRAS G12 mutations, announced 23 June 2025. An expanded access programme launched 1 May 2026, making the drug available free of charge to eligible patients who cannot enrol in an ongoing trial.
Jobs traces the KRAS story back a decade, to scientists at Amgen finding a cryptic pocket in what had been described as a smooth, featureless protein surface. That pocket gave rise to Lumakras, the first approved drug against a KRAS mutation, targeting only one specific variant. AI, Jobs argues, has since mapped the remaining variants and suggested new blocking strategies, opening a target that oncology had essentially written off.
Beyond KRAS: p53, Epigenetics, and What Yosemite Is Building
Three Yosemite companies are pursuing p53, the tumour suppressor gene that nearly every human cancer disables. Jobs says the firm believes it has found a shared surface marker across p53’s many mutated forms, which would make it possible to attack them in bulk rather than one variant at a time. It has never been done.
Tune Therapeutics, another portfolio company, is applying epigenetic editing to hepatitis B, which affects more than 250 million people and is the primary driver of liver cancer. The approach adds or removes methyl groups at specific DNA sites to silence the virus, mimicking what the roughly 1% of patients who clear the infection spontaneously appear to do naturally. Histosonics, an outlier in the portfolio for being a device company, uses histotripsy to destroy liver and pancreatic tumours without incisions, collapsing microscopic air bubbles at precise locations in tissue.
On AI, Jobs is measured. The technology is accelerating grunt work, he says, reproducibly and at speed, and it has helped identify druggable pockets in proteins that chemistry alone could not reach. Historically, roughly 15% of the genome was considered accessible to drugs; protein-protein interactions were simply too complex to target. That proportion is growing, partly through AI-assisted discovery.
For clinical trials, he sees the most transformative near-term application in synthetic control arms, where existing patient data substitute for a recruited comparison group. A Phase 3 cancer trial costs around $260 million and succeeds only one in three times; halving the recruitment burden would materially change both economics and speed. The FDA, Jobs notes, is actively engaging with the approach.
The one structural risk he flags has not gone away: NIH funding pressure. A proposed 40% budget cut, unprecedented in the agency’s history (the largest prior cut was 1% in 2009, which eliminated 7,000 positions), was rejected by Congress on a broadly bipartisan basis. A 12% cut has since been proposed. Jobs expects the same rejection, and says his own preference would be to increase the NIH budget to something approaching $100 billion, given that on an inflation-adjusted basis it has effectively contracted over the past decade.
Two companies across both funds have failed for scientific reasons, which Jobs frames as exactly the expected outcome for a firm making bets at the preclinical stage. The rest of the portfolio is, by his account, moving faster than he anticipated when Yosemite launched. The oncogenes that defined a generation of failed drug discovery, KRAS, Myc, beta-catenin, p53, are now, in his view, within reach. The question is who gets there first.
