Reed Jobs on Cancer, AI, and Yosemite: Why He Prefers Breakthroughs to His Last Name
Reed Jobs on Cancer, AI, and Yosemite: Why He Prefers Breakthroughs to His Last Name
By Decode Today News
Reed Jobs, the founder of Yosemite, an oncology-focused venture firm, is making waves in the biotech world not for his famous surname, but for his relentless drive to cure cancer. His firm, launched in 2023, is redefining how early academic research translates into groundbreaking therapies, utilizing a unique blend of philanthropy and venture capital, now supercharged by the rapidly evolving capabilities of artificial intelligence (AI). Jobs, a self-deprecating and highly engaged conversationalist, is far more keen to discuss the intricacies of drug discovery and clinical trial design than the legacy of his father.Yosemite's Mission: AI-Driven Oncology and Novel Drug Discovery
Yosemite is uniquely positioned in the biotech landscape, dedicated exclusively to oncology, a sector representing 40% of the entire biotech industry. The firm's distinctive approach involves actively building biotech companies from the ground up, originating from nascent academic research, rather than solely investing in existing ventures. This model leverages philanthropy to de-risk early, "gentle" ideas emerging from university labs, paving the way for cutting-edge science to advance into clinical development. The integration of AI is proving to be a game-changer, accelerating drug discovery and optimizing clinical trials at an unprecedented pace.Three years since its inception, Yosemite has grown into a formidable player with a team of 17, recently announcing the first close of its second fund, targeting an ambitious $350 million. This growth comes amidst a significant shift in the biotech investment climate, characterized by renewed interest and a surge in pharmaceutical acquisitions. Jobs highlights the expanding opportunities, particularly as a cluster of blockbuster drugs face patent expiration, opening new avenues for innovative treatments.
A significant portion of Yosemite's second fund, about a third, is dedicated to creating its own companies, either based on internal ideas or developed in collaboration with leading academic institutions like Yale, Berkeley, and Stanford. The remaining two-thirds are invested in promising companies founded by others. Crucially, Yosemite also allocates 2.5% of its assets under management, along with an additional $1 million annually from management fees, into a donor-advised fund. This fund provides no-strings-attached grants, directly contributing to the foundational research that often sparks new company creation, as evidenced by two companies in their first fund originating directly from such grants.
Pioneering New Medical Frontiers and Market Evolution
Yosemite aims to create entirely new areas of medicine. Jobs proudly points to his team's pioneering efforts in epigenetic gene editing – a technology that modulates gene expression without altering the underlying DNA – and the safe, targeted delivery of gene editing to specific cells, a long-standing bottleneck in the field. This capability to be first in discovering novel therapeutic avenues is a core value proposition for prospective limited partners (LPs).
The biotech investment landscape has undergone a dramatic transformation since Yosemite's launch in 2023. At that time, the biotech index (XBI) was significantly down from its 2021 peaks, and pharmaceutical companies were not yet acquisitive. However, a confluence of factors has reignited investor confidence: improved interest rates, the looming "patent cliff" representing the largest in pharmaceutical history, and record cash reserves held by pharma giants post-pandemic. This has led to a significant acquisitive spree over the last eight to ten months, marked by multi-billion-dollar exits like Eli Lilly's acquisition of Kelonia for $7 billion, and major advancements in antibody drug conjugates.
A compelling example of recent breakthroughs is Revolution Medicines' work on KRAS, a cancer-driving gene long considered "undruggable." Their efforts in pancreatic cancer have impressively doubled the survival rate for the most common form of the disease, from 12 to 24 months, a development that has occurred only in the past year.
Advocacy for NIH Funding and the Role of Government
Reed Jobs has been a vocal advocate for robust NIH funding, expressing concerns over proposed federal cuts. While pressure from the government persists, it is less of a long-term threat than initially feared. Jobs highlighted that, historically, the largest NIH budget cut was 1% in 2009, costing 7,000 scientists their jobs. An administration's unprecedented request for a 40% cut last year was, thankfully, rejected by a bipartisan Senate and House. This year's proposal for a 12% cut, still substantial, is also expected to face similar rejection, given the NIH's over 90% public approval rating. Jobs believes the U.S. should go on offense, advocating for an increase to around $100 billion, noting that the NIH budget has effectively shrunk relative to inflation over the past decade.
AI: Reimagining Healthcare Delivery and Drug Discovery
For Reed Jobs, the collision of AI with drug discovery and clinical trial design is expanding opportunities faster than anticipated. AI's impact is already tangible across various facets of healthcare. Hospitals, often technologically behind other sectors, still rely on antiquated systems like fax machines and floppy disks. AI is poised to revolutionize areas such as 24/7 call centers (like 911 triage), electronic health records, radiology, and pathology.
However, where AI truly captures Jobs' interest is in clinical trials, which represent the biggest cost and time sink in drug development. A Phase 3 cancer trial alone can cost around $260 million with only a one-in-three success rate. Patient recruitment and retention are the largest expenses. AI offers the potential to create "synthetic control arms"—computer-generated stand-ins for untreated comparison groups, built from existing patient data. This innovation could halve the number of patients needed for trials and dramatically accelerate development, a concept the FDA is actively embracing.
Regarding AI in drug discovery, Jobs dismisses any notion of it being overhyped. He sees it as a "fantastic advancement" that democratizes science and accelerates processes. AI excels at rapidly performing "grunt work" with reproducible outcomes, often doing it incredibly fast. More profoundly, AI has been instrumental in identifying previously "undruggable" pockets in proteins. Historically, only about 15% of the genome was considered druggable because the chemistry for targeting protein-protein interactions was too complex. This has changed dramatically, hand-in-hand with AI.
The success of Revolution Medicines in targeting KRAS, a protein once deemed a "death star" due to its smooth, featureless surface, illustrates AI's power. While scientists at Amgen initially found a cryptic pocket leading to the first KRAS drug, Lumakras, AI has since identified other variants and creative new ways to block it, significantly broadening the therapeutic potential.
Yosemite's Bold Targets: p53 and Beyond
Yosemite is tackling some of the most challenging targets in cancer, including the "biggest one of all": p53. This tumor suppressor gene is famously abundant in elephants, which rarely get cancer, while humans have only one copy, easily compromised. p53 is the most frequently suppressed gene across human cancers; virtually every cancer must deactivate it to survive. If p53 could be reactivated or its mutated forms attacked, it would be a major Achilles' heel for cancer, a feat never before achieved. Jobs believes Yosemite has identified a way to hit an exposed marker across various p53 mutations.
Other notable portfolio companies include:
- Azalea: Born from a grant to Jennifer Doudna's lab, this company is now in the clinic.
- Quarry: Built with serial founder Craig Crews, Quarry focuses on "induced proximity," a novel therapeutic approach where a drug physically brings a disease-causing protein next to the cell's natural breakdown system.
- Tune: A premier epigenetic editing company in clinical development, targeting Hepatitis B, which affects over 250 million people and is a primary driver of liver cancer. Tune's technology adds or removes methyl groups to DNA, acting like a dimmer switch for gene activity. This approach aims to methylate and silence the Hepatitis B virus itself, mimicking the natural clearance mechanism seen in about 1% of spontaneously recovering individuals.
- Histosonics: An unusual device company for Yosemite, Histosonics uses histotripsy at scale for non-invasive liver tumor destruction. This technology employs ultrasound-like waves to create and collapse small air pockets, precisely destroying tissue. Its lead programs focus on pancreatic and liver tumors, a natural pairing given that most pancreatic cancers metastasize to the liver.
Navigating Failures, Founder Relations, and The Bigger Picture
With close to 25 companies across both funds, Yosemite acknowledges that not every venture will succeed. Jobs notes that two companies haven't worked out for scientific reasons, an expected outcome when making early, tranches investments against scientific milestones. This approach allows for learning and adaptation.
Jobs advises founders considering large checks from big pharma to view such partnerships as "moving targets" because pharmaceutical priorities can shift dramatically with leadership changes. He emphasizes the importance of staying attuned to which companies are genuinely active in specific therapeutic areas. Yosemite maintains an "open door" policy for founders. When evaluating grants and companies, the firm removes CVs to avoid bias, funding both Nobel laureate labs and first-time grant recipients. They consider all modalities – small molecules, radiopharmaceuticals, gene therapy, immunotherapy, AI, and digital health – welcoming any idea that can impact cancer patients.
Storytelling, even in biotech, is crucial. Jobs has witnessed promising science fail due to poor communication from a CEO. He notes that often, the academic founder (chief scientist or medical officer) and the professional CEO (responsible for fundraising and narrative) are distinct roles, a division of labor that often works well.
The biggest surprise for Jobs in his three years running Yosemite has been the rise of GLP-1 drugs, leading to Eli Lilly becoming the first trillion-dollar pharmaceutical company. Beyond their primary use for weight loss, GLP-1s are showing early signs of being protective against neurodegenerative diseases and cancer, independent of weight loss. This highlights obesity as a "pan-disease" risk factor, alongside smoking, influencing multiple health outcomes.
FAQ: Yosemite and the Future of Cancer Treatment
What is Yosemite's core mission?
Yosemite's core mission is to cure cancer by building biotech companies from early academic research, exclusively focusing on oncology. It de-risks initial ideas using a blend of venture capital and philanthropic grants, actively creating new areas of medicine.
How does AI influence cancer research at Yosemite?
AI is a huge part of Yosemite's strategy, accelerating drug discovery by performing grunt work incredibly fast and reproducibly. It also helps find previously "undruggable" protein pockets and revolutionize clinical trials by creating synthetic control arms to reduce patient recruitment needs and speed up development.
What specific cancer targets is Yosemite pursuing?
Yosemite is aggressively targeting p53, the most frequently suppressed gene across human cancers, with multiple strategies across three companies. They are also developing therapies for KRAS mutations, Hepatitis B (a liver cancer driver), and using histotripsy for liver and pancreatic tumors.
What is the "patent cliff" and why is it significant for biotech?
The "patent cliff" refers to the period when a large number of blockbuster pharmaceutical drugs lose their patent protection, allowing generic versions to enter the market. This is significant for biotech because it creates immense pressure and opportunity for pharmaceutical companies, who, sitting on record cash reserves, are increasingly acquiring innovative biotech firms like Yosemite's portfolio companies to replenish their pipelines with new, patented therapies.
The Bigger Picture: A New Era of Cancer Innovation
Reed Jobs' Yosemite is not just another venture fund; it represents a forward-thinking model for confronting one of humanity's most persistent challenges. By actively building companies from foundational science, integrating cutting-edge AI, and strategically navigating the complex landscape of biotech investment and philanthropy, Jobs and his team are charting a course toward unprecedented breakthroughs. Their focus on historically "undruggable" targets and innovative therapeutic modalities, coupled with a deep understanding of market dynamics and a commitment to open science, positions Yosemite at the forefront of a new era in cancer treatment. The potential for these innovations, driven by both human ingenuity and artificial intelligence, to globally impact patient outcomes offers a powerful vision for the future of medicine.
