Reed Jobs is quite personable. He talks a lot, is self-effacing, often makes video-game references, and has a genuine passion for his work. While he isn’t eager to dwell on being the son of Steve Jobs, he also doesn’t shy away from it. When our producer, Maggie, inquired if he was using a MacBook during our video call on Thursday morning, he responded instantly: “Are you serious?”

What he prefers to discuss is Yosemite, the oncology-centric venture firm he founded in 2023 to, among other things, develop biotech firms from the ground up based on initial academic research, combining philanthropy with external investment capital. Three years later, Jobs is determined to elevate Yosemite to a major player, not merely for the sake of competition but because he believes the prospects ahead of him are growing more rapidly than he anticipated, thanks to AI influencing both drug discovery and clinical trial methodologies.

Companies in his portfolio that he takes the most pride in include Azalea, which originated from a grant to Jennifer Doudna’s lab and is now in clinical trials, and Quarry, a venture co-founded with serial entrepreneur Craig Crews that revolves around a novel therapeutic method known as induced proximity, where a drug functions by physically adjacent a disease-inducing protein to the cell’s own degradation system (instead of attempting to obstruct it directly).

The last time we connected with Jobs at TechCrunch Disrupt nearly three years ago, Yosemite was freshly launched, and the biotech sector was still reeling from its post-pandemic downturn. Now, the firm employs 17 people; a wave of significant drugs are nearing the end of their patent protections almost simultaneously, creating numerous new opportunities; and AI has transitioned from a mere curiosity to, in Jobs’s own words, a central component of Yosemite’s operations. We discussed all of this.

This Q&A has been shortened for brevity.

TC: Earlier this year, you announced the initial close of your second fund aiming for $350 million. What’s the current status at Yosemite?

RJ: It’s a period of intense activity for us. We’ve experienced remarkable traction and onboarded many significant new partners. Yosemite stands out as a venture entity for two main reasons: we focus exclusively on oncology — that represents 40% of the biotech landscape — and we aim to create our own companies. We’re convinced that cancer cures aren’t just waiting to be discovered in pharma; we need to innovatively create them using new insights. To mitigate risks on those concepts early on, while they’re still nascent in university labs, we apply some philanthropy without any strings attached. Two of the 20 companies in our first fund arose directly from a grant.

What portion of that $350 million is allocated to companies you’re establishing versus those you’re participating in?

Approximately a third is dedicated to companies we’re creating ourselves — either based on our own ideas or in collaboration with academics at institutions like Yale, Berkeley, and Stanford. This process requires considerable time and effort, which is why it only comprises a third. The remaining amount is directed towards existing companies which we aim to join. Furthermore, 2.5% of the fund’s [assets under management] will be allocated to a donor-advised fund — that’s completely unrestricted grant money, along with $1 million annually from our management fees.

Though it’s early, what arguments do you present to potential LPs about performance compared to other life science VC firms?

We are still in the early stages, but Yosemite is positioned to establish new medical domains ahead of other firms. My team has been at the forefront of a few of these: epigenetic gene editing [technology that modifies how strongly a gene is expressed, without changing the actual DNA sequence], and safe delivery for gene editing to targeted cells — a long-standing challenge in the entire field. If your goal is to be a pioneer and assist in uncovering new zones, that’s where our strengths lie.

Previously, you expressed concerns regarding the cautious nature of biotech investors. Has that situation changed?

It has indeed. When I established Yosemite in 2023, the XBI [ETF/index] was still significantly down from its peaks in 2021, and pharmaceutical companies hadn’t begun making acquisitions yet. The last three years have seen: improving interest rates and pharma facing its most significant patent cliff in history while holding substantial cash reserves from the pandemic. This has culminated in an acquisition surge over the past eight months. We’ve seen remarkable exits, such as Eli Lilly purchasing Kelonia for $7 billion, and significant victories in antibody-drug conjugates. A notable example: Revolution Medicines, addressing KRAS [one of the most frequently mutated cancer-driving genes, which was long deemed nearly impossible to target with drugs] in pancreatic cancer, has doubled the survival rate for [the most prevalent form of pancreatic cancer] — from 12 to 24 months. This progress has all been achieved within the last year.

Last year, you publicly voiced concerns over proposed NIH budget cuts.

Regrettably, federal government pressure remains, though it’s less of a long-term threat than it once was. Last year, historically, an administration sought cuts of up to 40% to the NIH budget. For reference, the largest previous cut was 1% in 2009, due to the global financial crisis, which resulted in 7,000 NIH scientists losing their jobs. Luckily, both the Senate and House — this is highly bipartisan — completely rejected the 40% cut. This year, they requested 12%, still the largest cut ever proposed by a significant margin, and I anticipate a similar dismissal. NIH funding enjoys over 90% approval. Personally, I advocate for an offensive approach — I’d boost it to around $100 billion. In dollar terms, it hasn’t grown in about ten years, so adjusted for inflation, it has actually diminished.

In which areas is AI currently influencing healthcare delivery?

American hospitals are among the most technologically backward sectors in the economy — a lot still relies on fax machines and floppy disks. An example is the call centers, akin to 911 triage, which are costly to maintain round-the-clock and are ripe for AI utilization. There’s also the realm of electronic health records, radiology, and pathology. However, my keen interest is in clinical trials — these represent the largest financial burden and time consumption in drug development. A Phase 3 cancer trial incurs about $260 million, with only one-third achieving success. The largest expense is patient recruitment and retention. AI could aid in constructing a synthetic control arm [a computer-generated substitute for the untreated comparison group, based on existing patient data], eliminating the need for a complete control group and potentially halving the required patient count while greatly enhancing speed. The FDA is currently encouraging this direction.

How about AI in drug discovery — is it overstated?

I believe it’s a terrific breakthrough, encouraging democratization of science and speeding processes up. Currently, AI accelerates much of the tedious work — not necessarily improving quality, but executing it at remarkable speeds with consistent results.

AI has [also] been effective in identifying areas we’ve previously struggled to access. Traditionally, we could only target about 15% of the genome because we faced challenges with proteins that interact with one another — the chemistry was too complex. This landscape has transformed over the past few years, closely following AI advancements. Consider Revolution Medicines: they pioneered the ability to target KRAS, which for decades lacked any [natural indentation for a drug molecule to attach and inhibit] — it’s essentially a smooth oval, akin to a death star. Roughly a decade ago, Amgen scientists discovered a peculiar hidden pocket within it, leading to the initial drug against it, Lumakras. This was effective only for one specific mutation; however, AI has since identified all the other variants we can now target and proposed innovative methods to inhibit it.

Which undruggable targets are your companies pursuing?

The largest target is p53. We’re tackling it with three companies employing different approaches. It’s a tumor suppressor gene — notably, elephants are largely cancer-free, and one hypothesis suggests they have many copies of p53, whereas humans possess only a single copy, making it easier to eliminate. p53 is the most commonly suppressed gene across human cancers; nearly all cancers must disable it to become viable initially. If we could reactivate it, or focus on its mutated forms, this might present a critical weakness in cancer, a feat that has yet to be achieved. We believe we’ve identified a way to target that exposed [marker] across the various mutations of p53.

Can you elaborate on Tune Therapeutics?

Tune has excelled as the leading epigenetic editing firm in clinical development for the past few years, focusing on hepatitis B, which impacts over 250 million individuals and is a primary contributor to liver cancer. This technology enables us to add or eliminate methyl groups [tiny chemical tags that attach to DNA and operate like dimmer switches, modulating a gene’s activity without altering the gene itself] at designated locations in the liver. Every cell within your body shares the same DNA but expresses it differently — consider gray hair: when melanin becomes methylated and deactivated, your body still produces hair, albeit less vibrantly. This mechanism is also responsible for aging immune systems and decreased metabolism. Hepatitis B appears foreign to your immune system, so we aim to methylate and deactivate the virus, mirroring the natural response of about 1% of individuals who spontaneously clear the virus.

Additionally, Histosonics is a device company, which seems atypical for Yosemite.

Correct, we don’t typically focus on devices. It’s the first firm employing histotripsy on a large scale for the destruction of liver tumors, utilizing noninvasive methods — it creates small air pockets and then collapses them to damage tissue in a very targeted manner, likened to an ultrasound rather than a CT scan. Their primary initiatives involve pancreatic and liver tumors — since most pancreatic cancer spreads to the liver, it’s a logical match. We anticipate this will play a significant role in treatment for both conditions.

What’s the current number of companies in your portfolio, and have there been any failures thus far?

Nearly 25 across both funds. Two have not succeeded due to scientific reasons — we evaluate these investments against scientific benchmarks, and given our early stage, sometimes failures occur on the scientific front. That’s to be expected.

What guidance do you offer founders considering a substantial investment from large pharmaceutical companies? You secure the funding, but it limits other alternatives.

Pharmaceutical companies are essential partners, but founders should view them as a variable — priorities can shift significantly with leadership changes. Following COVID, many pharma corporations, like Pfizer, incurred losses in infectious disease and exited the field entirely. Staying updated on who is actively involved in your domain is likely the most crucial aspect.

How can aspiring founders engage with you?

We maintain an open-door policy. When reviewing grants and companies, we remove any identifiers from people’s CVs — I prefer not to know whose idea it is or what position someone holds. We’ve supported labs led by Nobel laureates and those with no prior grant experience equally. We consider all modalities — small molecules, radiopharmaceuticals, gene therapy, immunotherapy, AI, digital health. Please reach out via email. Any concept capable of impacting cancer patients interests us.

Is storytelling as vital for biotech founders as it is in other sectors?

Regrettably, it is — I’ve observed companies with excellent science fail due to poor storytelling from their CEOs. However, typically, the founder and CEO are not the same individual. Founders often come from academia, serving as the chief scientist or chief medical officer, while the CEO is a professional operator responsible for fundraising and narrative construction. This division of roles tends to be effective.

Three years into leading Yosemite, what’s been your most significant surprise?

We now have our first trillion-dollar pharmaceutical company, Eli Lilly, due to GLP-1s — the top-selling drug category globally. We’re also observing initial indications that GLP-1s may offer protection against neurodegenerative diseases and cancer, beyond merely facilitating weight loss, as obesity is one of the two leading “pan-disease” risk factors — the other being smoking — that elevate the risk across nearly all disease categories. This has sparked renewed interest, ambition, and investment in vast disease territories that had become stagnant. Genes such as KRAS, Myc, beta-catenin, and p53 — the pantheon of oncogenes that have eluded us for years — are now, in our view, attainable. I didn’t foresee Yosemite progressing at this pace. This moment is more crucial than I initially realized, making it both more daunting and more empowering.

Before we conclude, what are your thoughts on the longevity sector?

I’m not ready to die anytime soon, and longevity is a personal priority. However, I believe we — like everyone else — lack a comprehensive understanding in this area. Ask a geneticist, and they’ll mention telomeres; consult an immunologist, and they’ll discuss T cells losing efficacy; a metabolomicist will have a completely different perspective. There isn’t a unified theory of aging analogous to what we have in physics. I don’t think there’s a singular “longevity problem”; rather, human bodies age differently across various cell types, and the interactions among these parts constitute what we term aging. Personalizing that optimization for each individual is precisely what healthcare ought to pursue, but I’m uncertain how to translate longevity into a one-size-fits-all commercial venture.