Reed Jobs comes across as very likable. He speaks quickly, makes self-deprecating remarks, draws comparisons to video games, and shows clear passion for his role. He avoids dwelling on being Steve Jobs's son yet handles questions about it calmly. When our producer Maggie inquired if he used a MacBook during our video interview on Thursday morning he replied without hesitation: "Are you kidding?"

He prefers focusing on Yosemite the oncology venture firm he started in 2023 partly to create biotech firms from early academic findings by blending philanthropic support with external capital. After three years Jobs aims to establish Yosemite as a key player driven by his desire to succeed and the accelerating opportunities from AI effects on drug discovery and trial design.

Among portfolio firms he highlights most are Azalea which originated from a grant to Jennifer Doudna's lab and has entered clinical stages and Quarry developed with serial founder Craig Crews using a new method called induced proximity where a drug physically brings a disease protein close to the cell's breakdown machinery rather than inhibiting it outright.

Our prior conversation with Jobs at TechCrunch Disrupt nearly three years earlier found Yosemite newly launched amid biotech recovery from the post-pandemic slump. The firm now has 17 staff members several blockbuster drugs approach patent loss in a similar timeframe generating opportunities and AI has evolved from an afterthought to a central component of Yosemite efforts per Jobs. We discussed these developments in detail.

This Q&A has been condensed for brevity.

TC: You revealed the initial close of your second fund targeting $350 million earlier this year. How would you describe the current situation at Yosemite?

RJ: Activity levels are very high at present. We have achieved strong momentum and added several key new partners. Yosemite stands out for two main reasons: exclusive focus on oncology which represents 40 percent of biotech and preference for building our own companies rather than relying on external ones. We believe cancer cures will not emerge from existing pharma pipelines but require creation using fresh insights. To reduce early risks for concepts still in university labs we provide small philanthropic grants with no conditions attached. Two of our 20 first-fund companies arose directly from such grants.

How is the $350 million allocated between self-created companies and those joined from outside?

Roughly one third supports firms we develop internally either from our concepts or collaborations with academics at institutions such as Yale Berkeley and Stanford. This demands significant effort which limits it to one third. The remainder invests in externally originated companies we choose to join. Additionally 2.5 percent of fund assets under management supports a donor-advised fund for unconditional grants along with $1 million annually from management fees.

Though early what performance arguments do you present to potential LPs compared to other life science venture firms?

Our track record remains preliminary yet Yosemite can establish new medical fields ahead of competitors. The team has advanced areas such as epigenetic gene editing which alters gene expression strength without modifying DNA sequences and safe targeted delivery of gene editing to specific cells addressing a decade-long field bottleneck. Those seeking to lead in discovering novel domains will find our strengths here.

Initially you expressed concerns about conservative tendencies among biotech investors. Has this shifted?

Yes it has. At Yosemite's 2023 launch the XBI index remained far below 2021 peaks and pharma had not yet turned acquisitive. Changes over three years include improved interest rates and pharma facing its largest patent cliff ever while holding record pandemic-era cash reserves spurring acquisitions in recent months. Notable examples include Eli Lilly's $7 billion purchase of Kelonia and successes in antibody drug conjugates such as Revolution Medicines advancing KRAS targeting in pancreatic cancer doubling survival from 12 to 24 months within the past year.

Last year you voiced worries regarding proposed NIH funding reductions.

Pressure from federal sources persists but poses less long-term risk than before. Last year an administration sought up to 40 percent NIH budget cuts for the first time historically. The largest prior reduction was 1 percent in 2009 amid the financial crisis resulting in 7000 scientist job losses. The Senate and House rejected the 40 percent proposal in a strongly bipartisan manner. This year a 12 percent cut was requested still unprecedented in scale and likely to face similar rejection. NIH funding enjoys over 90 percent approval. I advocate increasing it to around $100 billion as it has not grown nominally in a decade and has declined relative to inflation.

In what areas is AI already transforming healthcare delivery?

US hospitals rank among the least tech-advanced sectors with much work still reliant on fax and floppy disks. Call centers such as 911 triage incur high 24/7 costs and suit AI applications. Electronic health records radiology and pathology also stand to benefit. Clinical trials interest me most as the primary expense and delay in drug development. A Phase 3 cancer trial averages $260 million with only one-third succeeding. Patient recruitment and retention drive the largest costs. AI could enable synthetic control arms using existing data to halve recruitment needs and accelerate timelines. The FDA is actively exploring this approach.

Is AI in drug discovery overhyped?

It represents a strong advance for broadening access to science and speeding processes. Currently AI accelerates routine tasks with consistent fast results rather than outperforming traditional methods. It has also identified previously inaccessible targets. Historically only about 15 percent of the genome was druggable due to challenges with protein-protein interactions. This has changed recently alongside AI advances. Revolution Medicines for instance became the first to target KRAS long viewed as undruggable due to its smooth surface. A decade ago Amgen identified a hidden pocket enabling Lumakras which addressed one mutation. AI has since mapped additional variants and innovative blocking strategies.

Which undruggable targets are your companies pursuing?

The primary one is p53 addressed via three companies and multiple approaches. As a tumor suppressor gene it explains why elephants rarely develop cancer possibly due to multiple copies versus humans' single copy which is vulnerable. p53 ranks as the most commonly inactivated gene in cancers since nearly all must disable it to develop. Reactivating it or targeting mutated forms could exploit a key cancer weakness never achieved before. We believe we have identified a common exposed marker across p53 mutation types.

Can you describe Tune Therapeutics?

Tune leads in epigenetic editing clinical programs targeting hepatitis B which impacts over 250 million people and drives liver cancer primarily. The approach adds or removes methyl groups at precise liver DNA sites acting like dimmer switches on gene activity without altering sequences. All body cells share identical DNA yet express it variably as seen in gray hair where melanin methylation reduces output while hair production continues. Similar mechanisms affect aging immunity and metabolism. Hepatitis B appears foreign so we aim to methylate and silence the virus mimicking natural clearance in about 1 percent of cases.

Histosonics operates as a device firm which differs from typical Yosemite investments.

Correct we rarely pursue devices. It pioneers large-scale histotripsy for noninvasive liver tumor ablation by forming and collapsing microscopic air pockets to target tissue precisely akin to ultrasound rather than CT imaging. Lead efforts address pancreatic and liver tumors with pancreatic cancer often spreading to the liver making this a logical fit. We anticipate it becoming central to treatments for both.

How many portfolio companies exist now and have any failed?

Nearly 25 across both funds. Two ended due to scientific issues as investments tie to milestones and early-stage work can fail scientifically as anticipated.

What guidance do you offer founders considering major pharma funding that may limit alternatives?

Pharma serves as an important ally yet founders should view it as dynamic since priorities vary with leadership changes. Post-COVID several firms exited infectious disease after losses such as Pfizer. Monitoring active players in one's field proves essential.

How might founders reach you?

We maintain an open policy. When reviewing grants and companies we disregard CV details to focus purely on ideas avoiding bias from names or titles. We have supported Nobel labs and first-time recipients equally. All modalities interest us including small molecules radiopharmaceuticals gene therapy immunotherapy AI and digital health. Contact us via email. Any concept benefiting cancer patients merits our attention.

Does storytelling hold equal importance for biotech founders as elsewhere?

Yes unfortunately some firms with strong science have faltered from poor CEO narratives. Often the founder serves as academic chief scientist or medical officer while a professional CEO handles capital raising and communication. This split functions effectively.

After three years leading Yosemite what has surprised you most?

Eli Lilly became the first trillion-dollar pharma firm thanks to GLP-1s the top-selling drug class globally. Early data suggest GLP-1s may guard against neurodegenerative conditions and cancer independently of weight effects since obesity ranks as one of two broad risk factors alongside smoking that elevate disease risks across categories. This has renewed focus ambition and funding on long-stagnant areas. Genes such as KRAS Myc beta-catenin and p53 once considered elusive now appear attainable. I did not foresee Yosemite advancing so quickly. The current moment carries greater weight than anticipated bringing both challenges and empowerment.