John Tsai, M.D., is rounding out his global drug development resume. After spending time at U.S. pharma giants Bristol Myers Squibb, Amgen and Pfizer—plus a four-year stint at Switzerland’s Novartis—he landed at Japanese company Daiichi Sankyo in April.
Immediately, the pharma veteran finds himself leading the R&D portion of the antibody-drug conjugate (ADC) specialist’s new five-year plan, which aims to lay the groundwork for Daiichi to become a global top 5 oncology company by 2035.
“There are definitely differences, not only in terms of the way that people look at science—the rigor and the perseverance at Daiichi Sankyo—but in addition to that, cultural differences of how we work,” Tsai said in an interview with Fierce on the sidelines of the 2026 American Society of Oncology annual meeting in Chicago this month.
To Tsai, the differences became obvious during his first earnings call at Daiichi, when the firm’s full-year results and five-year strategy were unveiled to investors.
“When you work at the pharma companies in the U.S. or in Europe, they’re much driven by the results quarter by quarter,” Tsai observed. “I see less of that [here].”
Instead, Daiichi looks to forecast “a longer-term view of what you are able to deliver, and it makes your job a little bit easier to do because you’re not managing quarter to quarter.”
Because executives don’t have to worry too much about maintaining personal credibility through delivering on every promise every quarter, they can aim high, Ken Keller, Daiichi’s head of global oncology business, added in the same interview.
But attention to long-term goals does not mean slacking on execution, Tsai argued.
“It allows you to actually not have those fire drills of delivering,” he said. “The urgency is still there, but the urgency is on a broader picture than a quarter-to-quarter basis.”
Balancing speed and biology
For Daiichi, speed, even measured in shorter timeframes, is no longer optional.
Unlike seven years ago, when the FDA first approved its AstraZeneca-partnered Enhertu, the ADC landscape has grown far more crowded. Rather than just a handful of players like Immunomedics, ImmunoGen and Seagen, all of which have since been acquired by Big Pharma, the field now features an array of clinical- and commercial-stage companies.
For Daiichi and its new head of R&D, the challenge is about outrunning the very gold rush the company helped ignite. And as a leader in the field, the question now is whether it can stay ahead of the game as a new wave of Chinese biotechs, similarly backed by major global partnerships, threatens to hem in the pioneer with their sheer numbers and R&D speed.
“We think about it every day,” Tsai said. “I’ve heard that there’s 200 ADC biotechs [in China]. But what you’ll see the way that these companies are advancing their ADC platforms is very similar targets in many ways and very similar approaches.”
About 200 ADC programs developed by Chinese companies have entered the clinic, with another nearly 800 in preclinical phase, according to life sciences data aggregator PharmaCube. Tapping into those candidates, Merck & Co. has a multi-asset collaboration with Kelun-Biotech, while GSK has repeatedly licensed from Hansoh, and BMS’ EGFRxHER3 bispecific ADC from Sichuan Biokin Pharmaceutical is on the verge of a first-in-class approval back in China.
Further, BioNTech has bought from Duality Biotherapeutics and MediLink, which is also partnered with Roche, and Pfizer’s recent $10.5 billion deal with Innovent Biologics includes ADCs, too.
“But the way we look at it, not only is it just to make sure that we’re executing very well, but we’re also thinking about it from a very rigorous standpoint,” Tsai said. “It’s rigor in the biology of what’s unique about that specific biology.”
Developing standout drugs against existing targets was exactly how Daiichi gained its initial success in the field. Enhertu was launched more than six years after Roche’s Kadcyla and has since beaten the Swiss company’s first-in-class HER2 ADC left and right. AstraZeneca-partnered Datroway landed on the U.S. market in 2025, about five years after Gilead’s rival TROP2 ADC, Trodelvy.
But even if Chinese companies do not embrace the same level of biological rigor as Daiichi, as Tsai suggests, when 200 strands of spaghetti are thrown at the wall, some might stick.
Now, Daiichi’s strategy has changed: break away from the pack by arriving first.
“We think about unique targets first, and we will be there first, because it’s novel approaches that we take,” he said. “It’s not repeating the sequencing of combinations of PD-1/VEGF. It’s novel approaches, and that’s what you’ll see in the pipeline.”
Because of how fierce the competition has become, Daiichi is holding its early projects very close to its chest.
“Sometimes people get a little frustrated when they talk to me, ‘why aren’t you disclosing your targets,’” Tsai said. “If we disclose them, then we will be in a race where we will have to move faster.”
Among the next wave of ADCs using Daiichi’s DXd platform, B7-H3-directed ifinatamab deruxtecan (I-DXd) is nearing a potential first-in-class FDA nod this October. CDH6-directed raludotatug deruxtecan (R-DXd) is also a potential first-in-class ADC and could report pivotal data in 2027. After a setback, HER3-targeted patritumab deruxtecan (HER3 DXd) is being delayed. All three products have been partnered with Merck.
But competition is keeping those races close. With strong early-phase results, BioNTech recently pushed its DualityBio-partnered B7-H3 candidate into phase 3 testing in metastatic castration-resistant prostate cancer, enrolling half as many patients as Daiichi’s rival study, potentially accelerating its challenge to I-DXd.
Similarly, Kelun and Merck’s latest sac-TMT data in non-small cell lung cancer have triggered best-in-class talk within the TROP2 class, just as Datroway’s first phase 3 readout in first-line NSCLC, Avanzar, is expected to read out this year.
Amid this competitive pressure, Daiichi is harnessing the power of artificial intelligence to develop specific biomarkers for its ADCs.
“While we’re still in the early stages, we have more data based on these ADCs than anyone else does,” Tsai said. “As we learn about these populations, we’re going to use them to enrich our trials to get better results, instead of saying, ‘Oh, all comers, we’ll just see what it looks like.’”
However, a biomarker-oriented approach to medicine may not always work to one’s advantage, especially if a rival drug can make life easier for doctors by covering a broader base of patients.
Daiichi and partner AZ have already incorporated an AI-enabled TROP2-based biomarker in their Datroway lung cancer trials, including Avanzar. But Keller acknowledged that digital pathology is not universally used and therefore will require “more of a heavy lift” from the commercial side. Doctors will be more motivated to adopt a biomarker strategy if the magnitude of benefit is notably bigger in the subpopulation than in the entire treatment group, he said.
New platforms
Within its new five-year plan, Daiichi aims to develop the next iterations of DXd, an ADC platform that has yielded multiple products. This includes work with novel payloads and other tumor-selective antibody engineering.
A big focus is understanding treatment resistance and cancer escape pathways, so the company can consider whether to combine or sequence drugs with different payloads, Tsai said.
An ADC candidate leveraging the immune system via a STING agonist payload is in phase 1 development. The company recently stopped internal development of a CLDN6 program but said data so far “confirmed the utility” of its modified pyrrolobenzodiazepine payload technology.
“We have two of the best partners in oncology, and we’ve learned a lot,” Keller said, referring to Daiichi’s collaborations with AZ and Merck. “The bar is really high for us to partner [on] our next set of assets.”
Tsai is optimistic that, with the help of AI, Daiichi can come up with at least two new platforms by 2030.
“Internally, we already prioritized some of these programs to come through earlier than 2030,” Tsai said. “I guess we’ll just have to wait to see what the data holds for us.”
Daiichi is not obsessed with keeping R&D innovation completely internal. Last fall, the Japanese pharma opened its third external research institute in San Diego, alongside two other locations in Boston and Munich, Germany. A business development team is embedded in China, where pharma giants have been busy plucking up promising R&D projects at a blistering pace.
Tsai is looking even beyond ADC and oncology into areas such as RNA interference, immunology and cardiovascular disease.
“While those look promising, it really has to be truly differentiated for us to move forward,” Tsai said.