Reed Jobs' Yosemite Targets $350M Second Fund as AI Collides with Cancer Drug Discovery
核心洞察
Yosemite (搜索), the oncology-focused venture firm founded by Reed Jobs in 2023, has announced the first close of its second fund targeting $350 million, with a team now numbering 17.
The firm builds biotech companies from scratch using a hybrid model of no-strings-attached philanthropy and venture capital, with about one-third of the fund dedicated to internally created companies.
Jobs highlights AI's transformative role in drug discovery, noting it has expanded the druggable genome beyond the historical 15% and is reshaping clinical trial design through innovations like synthetic control arms.
Reed Jobs, founder of the oncology-focused venture firm Yosemite (搜索), announced the first close of the firm's second fund earlier this year, targeting $350 million. Speaking in a wide-ranging interview, Jobs detailed how the firm — now with a team of 17 — is positioning itself at the intersection of artificial intelligence and cancer drug development, building companies from early academic research through a distinctive hybrid model that blends philanthropy with traditional venture capital.
"Yosemite (搜索) is a unique venture organization for two reasons: we only work in oncology — that's 40% of biotech — and we like to make our own companies ourselves," Jobs said. "We don't think the cures for cancer are sitting out in pharma waiting to be discovered; we think we need to go make them with new knowledge."
A dual-structure funding model
Yosemite (搜索)'s approach allocates approximately one-third of its fund to companies built internally — either from the firm's own ideas or in collaboration with academics at institutions including Yale, Berkeley, and Stanford. The remaining capital goes into externally founded companies that Yosemite joins as an investor. Additionally, 2.5% of the fund's assets under management flow into a donor-advised fund providing completely no-strings-attached grant money, supplemented by $1 million annually from management fees.
This philanthropic component serves a specific strategic purpose: de-risking early-stage ideas while they remain nascent concepts in university laboratories. Two of the 20 companies from Yosemite (搜索)'s first fund emerged directly from such grants. The portfolio now stands at close to 25 companies across both funds, with two having failed for scientific reasons — an outcome Jobs characterized as expected given the early-stage nature of the investments.
AI's expanding role in oncology R&D
Jobs described AI's integration into drug discovery and development as a "fantastic advancement" that has moved from a curiosity to a central component of Yosemite (搜索)'s operations. He pointed to two areas where AI is having particular impact: expanding the druggable genome and transforming clinical trial design.
Historically, only about 15% of the genome was considered druggable because targeting protein-protein interactions posed insurmountable chemistry challenges. "That's changed in the last couple of years, hand in hand with AI," Jobs said. He cited Revolution Medicines as a case study: the company successfully targeted KRAS (搜索), a notoriously difficult oncogene long considered a "death star" due to its smooth, pocketless surface. While Amgen scientists discovered a cryptic pocket in KRAS roughly a decade ago, leading to the first drug Lumakras, that therapy only addressed one specific mutation. "What AI has done is find all the other variants we can now target and show creative new ways to block it."
In clinical trials, Jobs highlighted the potential for AI-generated synthetic control arms — computer-generated stand-ins for untreated comparison groups built from existing patient data. This approach could halve the number of patients needed for a trial, dramatically accelerating timelines. A Phase 3 cancer trial currently costs approximately $260 million, with only one in three succeeding, and patient recruitment and retention represent the largest cost drivers. "The FDA is leaning into this right now," Jobs noted.
Targeting the undruggable: p53 and beyond
Yosemite (搜索) is pursuing what Jobs described as "the biggest one of all" among undruggable targets: p53, the tumor suppressor gene that is the most frequently suppressed gene across human cancers. The firm is approaching p53 through three different portfolio companies employing multiple strategies.
"Almost every cancer has to knock it out to exist in the first place," Jobs explained. "If we could turn it back on, or attack its mutated forms, that's one of cancer's Achilles' heels, and it's never been done." He indicated the firm believes it has identified a way to hit an exposed marker across the various ways p53 gets mutated.
Among Yosemite (搜索)'s portfolio highlights, Jobs pointed to Tune Therapeutics (搜索), which he described as "the premier epigenetic editing company in clinical development." Tune is targeting hepatitis B (搜索) — a virus affecting over 250 million people and the primary driver of liver cancer (搜索) — using technology that adds or removes methyl groups at specific sites in the liver to silence the virus. The approach mimics the natural mechanism observed in approximately 1% of people who spontaneously clear the virus.
Another portfolio company, Histosonics (搜索), represents an unusual investment for Yosemite (搜索) as a device company. It employs histotripsy, a noninvasive therapy that creates and collapses small air pockets to destroy tissue in targeted areas, similar to ultrasound rather than CT scanning. Lead programs focus on pancreatic and liver tumors, a natural pairing given that most pancreatic cancer (搜索) metastasizes to the liver.
A shifting biotech landscape
Jobs characterized the current investment environment as markedly improved from 2023, when Yosemite (搜索) launched amid a post-pandemic biotech downturn. "Pharma is entering its largest patent cliff in history while sitting on record cash reserves from the pandemic," he said, pointing to an acquisitive spree over the preceding eight months that included Eli Lilly's $7 billion acquisition of Kelonia.
He also highlighted clinical progress in pancreatic cancer (搜索), where Revolution Medicines' KRAS (搜索)-targeting approach has doubled survival rates for the most common form of the disease — from 12 to 24 months.
On the policy front, Jobs expressed cautious optimism regarding NIH funding, noting that while the administration had proposed unprecedented cuts — 40% last year and 12% this year — bipartisan congressional support has consistently rejected these reductions. "NIH funding has more than 90% approval," he said, advocating instead for increasing the NIH budget to approximately $100 billion.
Looking ahead, Jobs pointed to GLP-1 drugs as an unexpected catalyst reshaping oncology ambition. With Eli Lilly becoming the first trillion-dollar pharmaceutical company on the strength of GLP-1s, and early signals suggesting these drugs may offer protective effects against neurodegenerative disease and cancer independent of weight loss, the field is attracting renewed capital and ambition. "Genes like KRAS (搜索), Myc, beta-catenin, and p53 — the pantheon of oncogenes that have evaded us for decades — are now, we think, within reach," Jobs said. "I didn't expect Yosemite (搜索) to be moving this fast."