John Oyler: Rewiring Operations in Oncology

In global biopharma, companies are often built around new molecular discoveries or innovative disease targets and therapeutic platform pursuits; while some plot their beginnings more closely around an operational model pathway.

The story and trajectory of BeOne Medicines, originally founded as BeiGene, a startup with employees in the U.S. and China, in 2010, may qualify as that rare combination of being both. Today, domiciled in Basel, Switzerland, after a mid-2025 rebrand, BeOne is perhaps one of the clearest examples of a modern global biotech built outside the traditional blueprint of legacy Western pharma.

The oncology drugmaker was founded with the vision of making cancer medicines more accessible by streamlining clinical trials. Steering the launch strategy was John Oyler, the Pittsburgh, Pennsylvania-raised MIT grad with entrepreneurial instincts honed at the likes of McKinsey & Company and Stanford Business School, and co-founder Xiaodong Wang, Ph.D., a Chinese-American scientist whose pioneering work identifying the molecular mechanisms of apoptosis (programmed cell death) established him as one of the most respected researchers in cancer biology.

With Wang representing the academic engine and Oyler the operating architecture, the duo started BeOne with the deliberate intention of not merely to discover hopeful and highly-sought breakthroughs in cancer, but to turn the entire apparatus of drug development and healthcare access on its side.

“One of the things we really realized was that medicine isn’t accessible to many patients,” Oyler, BeOne’s CEO and chairman, reflects in an interview with Pharmaceutical Executive. “You go to all this work, you figure out something is safe and it’s efficacious; it can help a bunch of patients, but it can’t get to them. And that was very frustrating to both of us.”

Oyler recalls the concerning statistics at the time related to treatment cost and access in cancer, including, for instance, U.S. patient struggles in covering drug copays, and, globally, the strikingly low percentage of patients actually receiving the most effective oncology medicines that were available.

“So we looked at that and said, why?” Oyler explains.

Thus, BeOne was born. In the nearly 16 years since, anchored by an R&D approach strictly — and purpose-built — around aligning speed, scale and efficiency, the former startup has grown into a multinational commercial-stage enterprise with more than 12,000 employees across operations in six continents, and a product reach into more than 75 countries and 2 million cancer patients. The company’s flagship medicine is Brukinsa (zanubrutinib), its oral BTK inhibitor for chronic lymphocytic leukemia (CLL) and other certain B-cell malignancies. The drug generated $3.9 billion in global sales in 2025 — the top seller, as well as owner of the broadest label, of any BTK inhibitor in its class.

Overall, BeOne’s revenue totaled $5.3 billion in 2025, a year-on-year surge of 40%. That translated, Oyler mentions, to a notable milestone for BeOne: The company achieved net profitability for the first time in its history, behind net income of approximately $287 million and free cash flow that was approaching $942 million. BeOne also boasts a pipeline of more than 35 assets in clinical development across hematology and multiple tumor types and modalities. Wang, meanwhile, has served as chairman of the organization’s scientific advisory board since 2011, and has been on the board of directors since 2016.

“You first have a vision, then you have to learn to crawl, then you have to learn to walk and then you learn to run,” Oyler tells Pharm Exec. “We’re year 16, so I think we’re kind of learning to drive at this point. But we can drive, and that’s a wonderful thing.”

The founding logic

In describing the impetus of BeOne’s formation, Oyler points to the often lofty figures industry experts attribute to the cost, on average, of bringing a novel medicine to the market. The popular number cited for many years has been roughly $2 billion; Oyler notes some today have even attached a $6 billion price tag. Wherever the true figure may actually fall, the purported totals, nevertheless, are “hard to believe,” Oyler remarks, and backed his opinion that the industry had spent too little time addressing the structural inefficiencies that determine whether certain innovations, though successfully developed, could reach the patients who need them most at scale.

A recognition drawn from his fundamental business training at McKinsey and Stanford, where he picked up an MBA, Oyler concluded that such disconnects in the system were not because the science didn’t translate, but because the economic cost and infrastructure associated with getting a drug approved were predominately front-loaded — and “almost entirely in clinical trials.”

“In reality, I knew from my experiences that to dose a patient with cancer was hundreds of thousands of dollars in a clinical trial, and that for many medicines to get approved, you had to dose 500, 1,000, maybe 2,000 patients,” says Oyler. “And then ultimately over time, as you figured out how the drug was working and where you might have a clinical program, that’s 5,000 to 10,000 patients. You could quickly do the math and see that these numbers to get a medicine approved are real.”

Digging deeper into the clinical component, the BeOne founders observed that the vast majority of studies were being conducted by third-party contract research organizations (CROs) and run largely at the most expensive medical centers in the wealthiest markets in the world.

“There weren’t many clinical trials being run at small rural oncology centers in the United States. And there wasn’t much being done in Latin America, for example,” Oyler tells Pharm Exec. “So what we realized is the costs keep escalating. There’s great science to do, there’s not enough patients, there’s expensive institutions — there’s probably a better way to do this.”

From there, Oyler helped chart a course to redesign the system at the core of how medicines are brought forward. Supporting this purpose was BeOne’s decision “from day one” to bypass the use of third-party CROs and, instead, work directly with the clinics and investigators itself.

“That would enable us to go out to these smaller, often not included centers and bring them into the clinical trial ecosystem, which is good not only for that trial, but forever, because they’ll be there for ourselves and all other people trying to make oncology medicines,” Oyler recounts on the reasoning behind the logic.

Beyond simply internalizing clinical operations, BeOne’s envisioned model also emphasized the development of its own proprietary technologies and tools. The dual aim was to bring new sites onboard efficiently, free them up to focus on patients most effectively and answer the same fundamental clinical questions significantly quicker and at a lower cost base: is a drug candidate efficacious? Is it safe? Does it meet various global regulatory requirements?

“That was the hope and belief. Of course, that was combined with ‘do great science,’” Oyler reminds. “My co-founder is a real scientist who is able to solve very intractable problems. That was always at the core of what we were trying to build. We didn’t want to just do great innovation for innovation’s sake. We wanted to do innovation that could actually reach patients.”

Paving the “superhighway”

In the years since, the company’s founding premise has been borne out through learned experience and “probably some of our own early stumbles,” Oyler acknowledges, both of which helped reveal the importance and potential of manufacturing as a strategic advantage BeOne could seize on “if we could control that system to be faster and to be lower cost,” the CEO adds.

Today, BeOne, with Brukinsa; another commercial therapy, Tevimbra, an anti-PD-1 monoclonal antibody approved in multiple indications globally; and a portfolio of dozens of investigational candidates, has a clinical and manufacturing operations network of roughly 6,000 people spread across six continents. That includes the company’s $800 million biologics manufacturing plant that opened near Princeton, New Jersey, in 2024, as well as facilities in Asia and Europe.

Leveraging these capabilities across R&D and manufacturing, BeOne refers to its in-house clinical engine as its global “superhighway.” According to Oyler, the network generates what the company believes is 30% faster development cycles vs. industry peers.

“That velocity is just not achievable” through a CRO- or contract development and manufacturing organization (CDMO)-dependent model, says Oyler. “This is a genuine competitive advantage for us.”

Functions such as patient enrollment and data collection are examples of areas where advantages can be realized. In the former, for instance, Oyler says the model can accelerate movement through different patient cohorts during dose escalation and for studying and understanding ways to expand into subpopulations or other indications. When applied to the data component, and broader speed and time considerations, the CEO points to the benefits of pushing boundaries in leveraging the company’s own management tools.

“It’s really hard when you have other organizations sitting between you using their own platforms and their own technology that you can’t control or interface as easily with,” he contends. “[The CROs and CDMOs] are good companies and they do very high-quality things in all of those spaces; it’s just they don’t always do them with the same sense of urgency or with a sense of focus on short-term and long-term cost. Both of those things are very important to a biotech company as it thinks about the return that they’re going to get on the investment they’re making.”

A profitable pivot

With, as mentioned, BeOne posting net profitability for the first time in 2025, the company, Oyler says, has completely shifted from its long path in investment mode to what he describes as “a durable, scalable, profitable company,” noting as well that BeOne, in February, set its total revenue guidance for full-year 2026 between $6.2 and $6.4 billion, which would be an increase of 17% to 21% from a year ago.

The “foundational engine” behind the shift, as Oyler terms it, is Brukinsa, which was originally granted accelerated approval by the FDA in late 2019 to treat adult patients with mantle cell lymphoma who received at least one prior therapy. The drug, designed for continuous and sustainable inhibition of BTK protein, has since added four approved indications, including the aforementioned CLL, as well as Waldenström’s macroglobulinemia, marginal zone lymphoma and follicular lymphoma.

At the most recent American Society of Hematology annual meeting last December, BeOne presented landmark six-year results from its phase 3 SEQUOIA trial evaluating Brukinsa in first-line CLL. The data demonstrated progression-free survival and overall survival of 74% and 84%, respectively.

“These results just continue to validate our scientific hypothesis,” says Oyler on BeOne’s belief, rooted in the Brukinsa program — where the drug, as then-investigational compound BGB-3111, achieved target identification in 2012 — that there were opportunities to deliver more specific inhibition against BTK, and improve the selectivity and absorption associated with first-generation BTK inhibitors. “If you’re fighting cancer, you’d rather have something fighting it every second, every moment, than from an on-and-off perspective.”

Illustrating that “follow the science” mentality has been Brukinsa’s aggressive expansion path. Unlike conventional approval strategies often built around easier comparator arms, BeOne chose to run its first phase 3 trial for Brukinsa in CLL in a head-to-head study against Imbruvica (ibrutinib), the class’s established, first-generation blockbuster agent.

“The goal was to show that it was more efficacious and safer, and we hit on both of those metrics statistically,” says Oyler, who credits the decision as BeOne’s proudest moment to date, resisting perhaps the safer road toward incremental gain in favor of a “bold and very unusual” route in industry circles.

“I think that was a tribute to doing the right thing scientifically and doing the right thing to ask the right scientific questions,” he adds. “Not that, ‘can you beat something that’s weak?’ But can you beat something that’s important?”

Such disciplines, Oyler says, continue to be guiding forces in BeOne R&D pursuits today, and major elements of the company’s cultural DNA.

“We think that if you are afraid, if you have fear of failure, that will kill innovation faster than any competitive threat,” he tells Pharm Exec.

Future bets

While the Brukinsa story may validate its risk-taking model, it will be BeOne’s pipeline, of course, that will dictate company impact and growth over the long-term.

Among BeOne’s current stable of R&D projects, which encompass small molecules, monoclonal antibodies, protein degraders and targeted therapies, Oyler first singles out sonrotoclax (BGB-11417), its next-generation BCL2 inhibitor. The candidate, which is a fixed-duration, all-oral regimen in combination with zanubrutinib, is in multiple global phase 3 trials for CLL and mantle cell lymphoma.

“We do believe that it’s potentially best in class relative to venetoclax,” says Oyler, referring to the branded drug Venclexta, the first-approved BCL2 inhibitor, which was cleared by the FDA in 2016.

He points to early clinical data demonstrating unusually strong depth of response with sonrotoclax. According to Oyler, 91% of CLL patients in BeOne’s fixed-duration study showed undetectable disease at 31 months, marking the highest progression-free survival rate compared to other venetoclax-based fixed-duration regimens in a comparable timeframe. Data supported a favorable safety profile as well, the CEO says.

“That’s really encouraging and illustrates the tremendous unmet need despite the treatment options that are already available,” Oyler adds. “In this area, we’ve also been able to see kinetic curves that show driving undetectable [minimal residual disease] in blood much more quickly than we’ve been able to see with other combinations of BCL2 and BTK inhibitors. It’s just dramatically different looking curves.”

Another asset and mechanism garnering particular excitement internally is BGB-16673, a BTK degrader designed to not just inhibit the BTK protein — as Brukinsa does — but to remove it altogether. The distinction could create a new option for patients who develop resistance to BTK inhibitors, which Oyler says is a significant unmet need in patients whose disease has progressed. BGB-16673 is currently in mid- and late-stage clinical trials across a host of blood cancers.

On the solid tumor front, BeOne is building a hopeful franchise spanning breast, lung and gastrointestinal cancers. According to Oyler, its zanidatamab collaboration with Zymeworks, a clinical-stage biotech based in Vancouver, in HER2-positive gastroesophageal adenocarcinoma has produced compelling overall survival data. In late April, the FDA granted priority review to Tevimbra, in combination with zanidatamab and chemotherapy, as a first-line treatment for that indication.

In addition, five BeOne internally developed solid tumor assets are now entering late-stage development.

“That breadth is really important because it positions the company for durable growth far beyond our hematology franchise,” notes Oyler.

Entrepreneurial voyage

Though perhaps with a tinge of serendipity sprinkled in, bridging the worlds of science and business, Oyler’s journey to starting BeOne may have been destined from his days as a mechanical engineering major at MIT. The Pittsburgh native recounts working at the school 20 hours a week “doing all sorts of odd jobs” before eventually launching his own company with his roommate, selling carpets, refrigerators, bookshelves and other dorm essentials to college students returning to Boston-area campuses.

“It was really my first attempt at owning and running a business, and I learned a lot the hard way,” says Oyler. “You learned how important supply chain and operations were when you didn’t thoughtfully unload a bunch of trucks with carpets and you had to spend eight hours reloading them. So you learned there was a lot more to know.”

The experience would inspire Oyler, post-graduation, to land a job as a management consultant at McKinsey, where he had the unique opportunity to learn from some of the individuals who built the firm, and enroll at the Stanford Graduate School of Business.

“I knew I wanted to be an entrepreneur, I knew that I loved science and I knew from my parents I wanted to do something that was going to help people that I cared about and could contribute in a meaningful way,” he says.

That perspective would soon hit hard personally for Oyler. While embarking on his first formal entrepreneurial pursuits, Oyler sadly lost three close friends to cancer in a short period of time. Those events would crystallize Oyler’s career mission. And after working as CEO and president for a series of startups, including founding Telephia, Inc., an information company that was ultimately acquired by The Nielsen Company, his path led him to BeiGene.

“I knew with certainty I wanted to fight for life, and I decided I wanted to fight cancer with Xiaodong,” Oyler tells Pharm Exec. “And we really have been committed to doing that ever since.”

It is an urgency that Oyler and his leadership team, he says, strive to continually embed in BeOne’s culture, which is spread out across more than 45 global offices. For instance, when onboarding new employees, Oyler says the company bakes in a clear fundamental mandate: enter with a willingness to challenge the status quo and the way you did things at your previous organizations.

“The entire model that we have — internalizing our clinical operations, building these globally inclusive trials — all of this required us to kind of reject the conventional way the industry was doing things,” he says. “Part of what we say in our orientation is the industry has not succeeded in doing great science in a way that’s great for patients, great for investors and is able to get these innovations broadly and accessibly to patients. So we need to change. I think there’s real tremendous buy-in to that as an organization.”

In the oncology setting, of course, cultivating that mindset mix of urgency, risk-taking and goal-setting takes on greater magnitude. “It’s everywhere you go,” Oyler reminds on cancer’s reach — citing specifically a recent office meeting he had with someone juggling the emotions of two loved ones dealing with the disease.

The CEO notes as well that when exposed to the patient dynamic directly in his business, clarity of purpose is sharpened to degrees that even the most seasoned or battle-tested leaders might not anticipate.

“Whatever urgency you think you have as an entrepreneur, it changes when you start to meet patients,” says Oyler. “You understand that you need urgency because cancer doesn’t wait. If we want to fight it and if we want to help those patients that we’re treating, we just need to be better and faster.”