Oncology R&D

Pharma’s first multi-specific antibody hit the market more than a decade ago. Now, the drug category is seeing a surge of interest as pharma companies and investors embrace the more-is-better approach for cancer or autoimmune diseases.

The msABs drug category, which includes bispecifics, builds on the therapeutic power of monoclonal antibodies by targeting two or more sites instead of one. 

The first bispecific therapy hit the market after the FDA OK’d Amgen’s Blincyto in 2014. Since then, a steady trickle of more than a dozen other bispecific drugs has followed. But several tri-specific and higher-order msAbs are being navigated through the pipeline.

This newer generation of drugs has ramped up industry interest, due to their results in the clinic and improved safety profiles and pharmacokinetics, according to a report from DNB//Back Bay. The field has already generated two blockbusters: Genentech’s Hemlibra, a hemophilia treatment, and Vabysmo, used to treat eye diseases. But more are expected to reach that billion-dollar threshold, said Peter Bak, a managing director at Back Bay Life Science Advisors and one of the report’s authors.

While all of the approved msAbs — aside from Hemlibra and Vabysmo — are cancer treatments, there’s been a sizable shift in the pipeline toward autoimmune disease, thanks in part to the head-turning successes seen with CAR-T cell therapies in this space. 

“Lupus is an area where there's been some interesting data generated by a couple academic groups, and now a lot of companies are rethinking their strategy,” said Bak. 

Experts believe that T cell engagers, which harness the immune system to target cancer cells, can also be used to tame the wayward B-cells that drive autoimmune disease. The hope is that these drugs will produce similar results to CAR-T, but at a lower cost, giving them a potential market advantage. In some cases, msAbs could treat patients who didn’t respond to these other treatments, Bak said. 

“In an area like systemic lupus erythematosus where there's not much activity, and there is pretty big unmet need, one could see it being used as a first line biologic,” he added. “It’s going to be very indication specific.” 

Investment influx

The potential to tap into this rising market with multibillion-dollar potential has drawn a flurry of investments. In the first half of 2025, immunology and inflammation msAb companies outraised oncology companies by $269 million, according to the report. 

Nearly 250 msAb candidates are now in trials, including 24 late-stage drugs, and dealmaking has accelerated. In fact, msAb-related transactions have been on par with antibody drug conjugates (180 vs. 192 deals, respectively) for about the last five years, according to the report.

Several companies are testing msAbs for autoimmune conditions. Roche’s Lunsumio, a CD20/CD3 bispecific, already approved for lymphoma, recently finished an early-stage trial in lupus, Bak noted. 

Amgen is testing Blincyto, its anti-CD19 x anti-CD3 bispecific T cell engager in phase 2 for both lupus with nephritis and refractory rheumatoid arthritis. Meanwhile, Cullinan Therapeutics’ bispecific T-cell engager, CLN-978, is in phase 1 trials for lupus and rheumatoid arthritis. Initial data from the Cullinan trials is expected in the first half of 2026. 

“The other asset that people are looking at that’s in late-stage development is MoonLake [Immunotherapeutics] bispecific against two forms of IL-17,” Bak said. 

Primary endpoint results for Moonlake’s phase 3 program for hidradenitis suppurativa, a chronic autoimmune skin condition, are expected this month. If all goes as planned the company could file for approval in mid-2026.

While interest in autoimmune research has accelerated, oncology indications are still garnering attention, including the bispecific and potential Keytruda rival, ivonescimab, which was developed by China-based Akeso and licensed to Summit Therapeutics. Companies are also exploring msAbs in neurology, neurodegenerative diseases and solid tumors. 

But there are manufacturing and drug-stability-related challenges to overcome. These drugs will also need to prove their clinical chops to ensure a competitive edge other rising modalities including radiopharmaceuticals, protein degraders, CAR-T cell therapies and ADCs.

“In hematology/oncology it’s already there. It’s very much a commercial market where people are trying to optimize the dosing profiles and how it’s being delivered to patients,” Bak said. 

As companies move through the clinic, they’re vying for market share in up-and-coming indications, including autoimmune diseases. 

“It’s very much a race to market right now,” he said.

In an industry driven by scientific curiosity and innovation, the notion that too much data could be a drawback is almost blasphemy. But with a single phase 3 trial now generating nearly six million data points, it may be time to pare down protocols, according to a new study. 

On average, nearly one-third of the information collected across 105 trials was either “non-core” or “non-essential, and more than half of that extra data came from patient surveys, according to the study, conducted by Tufts Center for the Study of Drug Development, Tufts University School of Medicine and TranCelerate Biopharma,

“The big takeaway here is … encouraging our clinical teams and protocol authors to think through the design decisions they make and how they may impact downstream site feasibility and site burden, and perhaps even most important, patient participation burden,” said Kenneth Getz, executive director of Tufts CSDD and the study’s lead author.

Clinical trials have become more challenging over the years, as scientists develop more advanced therapies for harder-to-treat diseases. Trial sites have also multiplied and spread globally, which has lengthened trial timelines, Getz said.

“No matter how hard we try to simplify our protocols, there are more and more demands,” he said. “We have not, as an industry, been able to get ahead of complexity. We're always playing catch up.”

A recent Nature study confirms this trend, finding that over the last 10 years, average trial complexity scores have increased by more than 10 percentage points. For every 10-percentage point increase, overall trial length increased by one-third.

Some challenges, such as new regulatory requirements, are unavoidable. Other trial-slowing factors are self-inflicted as companies push for more data points without considering the drawbacks. There’s always a temptation to find out more. 

“Often when [companies] know a patient is filling out a questionnaire, [they think] let's just add a few more questions. Let’s conduct the questionnaire more frequently,” Getz said. “It may inform our understanding of the quality of life for the patient or their attitudes and perceptions. But it's a big burden when patients are filling out three questionnaires a day.”

Many of the phase 2 and phase 3 protocols reviewed in the study collected an overload of lower-priority information or data that will only be useful later on. 

“Companies may be gathering data on biomarker information or ways to target a more narrowly defined patient community. They gather some data to help with the positioning of the drug in the product label once it enters the marketplace,” Getz said. 

In addition, many of the trials included in the study, which were run by 15 different biopharma companies, included non-core procedures that didn’t support primary or secondary endpoints. These procedures accounted for up to 32.5% of phase 3 data collected per person, and 25% to 30% of the total burden on trial participants and research sites. 

“Some [of] the non-essential procedures may be conducted excessively. Did we need to collect that data on visits four, five, six, seven, eight, and nine when we only needed the data for visits four, five and nine,” Getz asked.

As protocols become increasingly byzantine, problems multiply. 

“The more complex, the more protocol deviations, the more protocol amendments, the slower the trial, the higher the dropout rates, and the slower the enrollment rates,” Getz said, adding that too many demands drive patients away and put a heavy burden on staff.  

Needed improvements

A primary goal of this study was to encourage protocol designers to be more thoughtful about what data to collect. 

“We need to elevate the urgency and the importance of doing this,” Getz said. “It's such a soft global economic environment for pharmaceutical and biotech companies. There's so much pressure on pricing.” 

Ultimately, Getz said he hopes the study sparks a discussion among protocol authors and clinical teams. TransCelerate’s member companies are now using study insights to develop a framework and toolkit, which could potentially be rolled out in early 2026, he said.

“It's so critical that we get our protocol designs right, that we optimize the design so that we don't really hinder this process,” Getz said.

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In oncology genomics, every sample is precious. Formalin-fixed paraffin-embedded (FFPE) tumor specimens—long considered the backbone of translational cancer research—are notoriously difficult to work with, often yielding degraded or chemically modified nucleic acids. However, in order to minimize errors and biases during DNA sequencing, high quality DNA libraries are needed for several important assays, such as, comprehensive genomic profiling (CGP), immuno-oncology studies, and biomarker discovery studies. A high-quality library provides uniform GC coverage, accurate representation of the input DNA, and is crucial for precise sequencing reads, especially when dealing with limited or degraded samples. Almost every tme, the difference between a successful sequencing run and one plagued by low or non-uniform coverage is caused by the use or lack of a robust, reliable, reproducible sample preparation workflow.

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In benchmarking studies performed in-house and with the Dana-Farber Cancer Institute Molecular Biology Core Facilities, truCOVER delivered improved genome coverage, higher library conversion rates, and improved SNP/INDEL detection accuracy compared with leading competitor workflows. This consistency extends across diverse sample types—including FFPE, blood, and saliva—making it ideal for translational oncology research where sample quality can vary widely.

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What could GLP-1s have to do with oncology? Potentially “everything,” according to Deborah Phippard, chief scientific officer at the mid-sized CRO Precision for Medicine.

Blockbuster drugs like Novo Nordisk’s Ozempic and Wegovy and Eli Lilly’s Mounjaro and Zepbound are so versatile in their effects that they could play a role in cancer as well as in diabetes, weight loss and cardiovascular conditions, Phippard said.

“These are some of the most complicated drugs I’ve seen in my career because they do so many things,” Phippard said. “The G protein-coupled receptor that a GLP-1 agonist binds to is at the top of so many different pathways, and there are so many downstream effects that feed back in.”

The FDA’s August approval of Wegovy for the liver disease metabolic-associated steatohepatitis, or MASH, is a testament to the drug’s ability to improve a condition by targeting underlying risk factors like weight — while also treating the disease through mechanisms the regulator acknowledged are not “fully understood.”

For the same reasons, GLP-1s could impact cancer patients as well, Phippard said. A large study in 1.6 million patients with Type 2 diabetes found that those receiving GLP-1s faced lower risk for many related cancers.

“If you’re obese and diabetic, you are at higher risk of any number of cancers, which is well-documented,” Phippard said. “Pancreatic, endometrial, ovarian and colorectal cancers in particular have been found to be driven by insulin resistance, so controlling obesity should theoretically take cancer incidents down.”

Beyond the benefits of weight loss to reduce cancer risk, the Swiss-army knife nature of GLP-1s could overlap with different pathways that govern how cancer forms and spreads from an immunological standpoint, she said.

“Looking at the function of specific T cells, NK cells, macrophages, dendritic cells, all of those functions you can demonstrably show change with a GLP-1 agonist,” Phippard said. “The MAP kinase pathway, the NF-kappa B pathway, VEGF — GLP-1 is upstream of all of these.”

The data around these pathways and the comorbidities associated with them is “messy,” Phippard acknowledged, but understanding clinical outcomes for patients being treated for cancer who are also on a GLP-1 could reveal actual effects.

GLP-1s and cancer therapy

Early research has shown that GLP-1s could potentially help overcome chemotherapy resistance, which would theoretically improve outcomes for cancer patients, though Phippard again noted the exact mechanism “isn’t brilliantly well understood.”

And with GLP-1s’ documented effects on the immune system, the drugs could also play a part in making PD-1 immunotherapies like Merck & Co.’s Keytruda or Bristol Myers Squibb’s Opdivo more effective, Phippard said.

“If you look at immune cells in an obese person, they don’t work that well and aren’t very healthy, but a GLP-1 can help,” Phippard said. “I’m always a little hesitant at that because the immune system is very complicated and massively redundant, but we should explore these areas further.”

Earlier in pharma’s GLP-1 era, some concerns that the drugs are linked to thyroid or pancreatic cancer arose, according to MD Anderson Cancer Center. But subsequent studies haven’t confirmed that connection.

Still, physicians are careful not to jump into the deep end with GLP-1s in an oncology setting, particularly with pancreatic cancer patients or those already suffering from nausea and vomiting, which a weight loss drug could exacerbate. Muscle loss is also associated with long-term GLP-1 use, which could make patients more frail over time.

Clinical studies for cancer are where GLP-1s could make a difference in how patients respond to certain drugs. With nearly 12% of all Americans having taken a GLP-1, the odds of patient overlap with clinical trials are growing, Phippard said, and researchers need to better understand those implications to ensure accurate data.

“We’re right at the beginning of how we work this out, but I think you’ve got to run a clinical study looking at this with a separate statistic even in its own right,” Phippard said. “I don’t think we’ll ever be able to pull it entirely apart, but I’m not planning on retiring anytime soon.”

A standalone oncology treatment?

As for whether GLP-1s would ever be considered a cancer treatment, that’s well down the road, Phippard said.

“We are not remotely close to a GLP-1 alone for cancer treatment,” she said. “There may be one or two patients who start a GLP-1 for whatever reason, and their immune system picks up, but that’s an anecdotal n of 1.”

But as a combination treatment alongside chemotherapy or immunotherapy, GLP-1s are a possibility.

Currently, “combo therapies are happening by accident” with patients both on a GLP-1 and undergoing cancer treatment at the same time, Phippard said. And companies like Lilly, which has a foot in both the diabetes and obesity market as well as oncology, could start thinking about the clinical opportunities without having to buy new assets.

“I’m expecting to see this coming out at all the big cancer meetings over the next five to 10 years,” Phippard said. “This is starting to buzz in the community.”

For AstraZeneca, a single mutation has launched an entire blockbuster lung cancer franchise.

In 2003, the pharma giant began a complicated journey that was almost doomed from the outset. The lung cancer treatment Iressa, which targeted the mutation of the EGFR gene, gained FDA approval, only to be pulled from the market two years later due to low efficacy.

But in the ensuing years, AstraZeneca learned more about the subset of the population that did respond to the medication, and by 2015 Iressa was re-approved based on studies in patients with EGFR mutations. Shortly thereafter, the company raked in the first approval for the next generation of EGFR-targeting lung cancer drugs with Tagrisso, now considered the “backbone” of its lung cancer portfolio.

The precision medicine approach renewed the company’s efforts in oncology that continue to this day. In a recently revealed study, Tagrisso with chemotherapy demonstrated long-term overall survival benefit in patients with EGFR-mutated non-small cell lung cancer. And AstraZeneca has built a franchise on EGFR — the recent approval of Datroway adds to the company’s prowess in lung cancer and contributes to the lofty goal of treating more than half of all patients with lung cancer by 2030.

Here, we spoke to vice president and head of AstraZeneca’s lung cancer programs, Arun Krishna, about how the company’s strategy has evolved to embrace a single mutation.

This interview has been edited for brevity and style.

PHARMAVOICE: How did EGFR become such an important mutation to target, from AstraZeneca’s perspective?

ARUN KRISHNA: Most people associate lung cancer with a smoker's disease, but we know very clearly that 20% of people who get lung cancer have actually never smoked. So our journey started with the whole EGFR space because we understood from the science that if you have an oncogenic driver like EGFR, that’s something that leads to lung cancer in nonsmokers. Ten years ago, we got our first approval with Tagrisso in [specific EGFR mutation] T790M, so we started with a very small population in second line, and quickly moved to first line with the Flaura study that showed overall survival benefit. Since then, Tagrisso has been the standard of care in EGFR.

We’re moving to identify lung cancer earlier. We [now] have EGFR data not just in the metastatic setting, but also in the early stage. Tagrisso is the backbone treatment for all EGFR patients across all stages of their cancer. Twenty years ago, the only option patients had was chemo. The science has evolved tremendously.

AstraZeneca has a slate of lung cancer drugs, Datroway being one of the latest approvals. What is the importance of having several drugs that target the same mutation?

There are different patient types, all within the EGFR space. Some of them might benefit from monotherapy. Some might benefit with a combination of treatments, because ultimately, that is where the future is going. There's not one single modality that addresses a specific type of cancer, so we are looking at multiple ways to attack the cancer through combinations of treatment. 

AstraZeneca has a goal to treat more than half of all people with lung cancer with one or more of its drugs by 2030. How will you accomplish that?

There's a [multi]-pronged approach to achieving this. One is through the medicines, making sure we are not just looking at single agents, but combinations. Secondly, we’re moving into the earlier part of the patient journey. But that isn't sufficient, because we know the rates of screening in lung cancer are very low, especially here in the U.S. There isn't a policy around screening for people who have never smoked. So one of our big goals in the next three to five years is to partner with health systems, partner with our clinical community, partner with patient advocacy groups to drive that awareness of screening. In addition, we’re working in collaboration with universities and academic centers to look at programs for nonsmokers so they can be detected earlier. It goes in tandem: You have the medicines that we’re discovering and moving into the clinic very quickly, but at the same time working in the environment to be able to rapidly drive the adoption of screening strategies in the population.

EGFR is now a well-established target for lung cancer, but that wasn’t always the case. Does the infrastructure still exist to make those kinds of leaps?

We are on the cutting edge, and we're in the center of that explosion of science and technology. We're going to discover more subtypes and mutations. But there’s still a gap, and that’s what needs to be addressed. We’ve come leaps and bounds, but there’s still work to be done at the grassroots level, at the community level, to make sure that clinicians are aware, and that patients ask to be tested for their biomarker so they then get the right treatment at the right time, and have the best survival outcome possible.

Deal announcements often showcase where the stars align in pharma around up-and-coming therapeutic areas, companies or technologies. On the flipside, breakups tend to reveal which stars are fading.

Given the high level of activity in the oncology R&D space, cancer is where many recent splits have recently occurred. Although the booming weight loss market has triggered a surge in cardiometabolic research, oncology is still king — and the industry has nearly 9,500 oncology drugs in its pipeline, according to Citeline analysts.

Neurology is pharma’s second largest R&D bucket, but still far behind cancer with about 3,900 drugs in the works.

And behind most broken partnerships lies a tale of bigger-picture R&D challenges faced by drug developers throughout the industry.

Here’s a look at some of biopharma’s most recent breakups in cancer care.

Genentech’s $2 billion divorce from Adaptive

Following a surge of enthusiasm for T cell-receptor therapies, setbacks have taken a toll.

Most recently, Genentech withdrew from a deal worth up to $2 billion with Adaptive Biotechnologies centered around TCR discovery tech. 

Like CAR-T cell therapies, TCR-based treatments harness a patient’s immune system — in this case, recognizing a different antigen — and have shown promise in cancer.

Big Pharma has jumped on the TCR bandwagon in recent years. AstraZeneca struck a $320 million deal with Neogene Therapeutics in 2022 to develop cell therapies. 

Last year, R&D efforts paid off when the FDA OK’d the first TCR therapy, which was given the go-ahead for metastatic synovial. Despite the historic approval, the drug’s developer, Adaptimmune Therapeutics, recently implemented dramatic cost-saving measures to focus on the drug’s launch, cutting over 60% of its staff and putting several cell therapy assets up for sale.

Now, once-promising partnerships for TCR therapies are being shelved.

AstraZeneca scrapped the lead TCR candidate with Neogene amid R&D restructuring that culled several cell therapies from its pipeline, the company stated in its most recent earnings report.

And after announcing a research pact with Genentech in 2019, Adaptive has now lost its powerhouse partner, an SEC filing from the biotech revealed this month. The multiyear collaboration produced an FDA acceptance of one clinical trial IND in 2023.

Adaptive plans to move ahead with TCR drug development.

But Genentech — and its parent company Roche — have made some moves away from immuno-oncology in general. Roche dropped two early-stage TCR candidates in 2023 and scrapped a $3 billion deal with Adaptimmune the following year. In addition to its retreat from the Adaptive tie-up, Genentech walked away from an immuno-oncology collaboration with Bicycle Therapeutics in July.

Ipsen slashes ADC deal with Sutro  

With the antibody-drug conjugate space heating up, Ipsen jumped into the arena last year in a deal with Sutro Biopharma worth up to $900 million. The tie-up focused on a candidate dubbed STRO-003 that targets the ROR1 tumor antigen, which is highly expressed in several blood and solid tumor cancers.

But France’s Ipsen has already backed away from the pact, Sutro disclosed in its latest earnings report, following “the review of new data and developments in the ROR1 landscape.”

While some ADCs have skyrocketed to blockbuster heights in recent years, clinical readouts for ROR1 candidates have been spotty.  

Late last year, Merck & Co. unveiled a splashy 100% response rate for its anti-ROR1 ADC in a phase 2 lymphoma study. Yet, the data also revealed potential safety concerns. Among the small cohort of patients, 58% experienced treatment-related adverse events.

Lyell Immunopharma also reported adverse events and one patient death in an early-stage trial for a ROR1-targeting CAR-T cell therapy last year.

Sutro, which is also developing drugs with Astellas Pharma and Vaxcyte, has also dropped STRO-003 from its pipeline, despite calling it a “well-engineered ADC candidate.”

Upcoming data from other companies could uncover more about the potential for ROR1-targeting ADCs. Earlier this year, Immunome dosed the first patient in a phase 1 for its ROR1-targeted ADC for advanced B-cell lymphomas and solid tumors.

Gilead waves goodbye to Arcus asset

Gilead Sciences struck a 10-year research collaboration with cancer-focused Arcus Biosciences in 2020 with the goal of bolstering its immuno-oncology pipeline. The partnership included candidates like antibody therapies targeting the PD-1 and TIGIT pathways. As promising clinical data rolled in, Gilead exercised options on three of Arcus’ programs the following year.

Now, the $725 million match-up is showing wear and tear.

Earlier this year, Gilead returned one of its drugs, etrumadenant, to Arcus. Despite meeting with the FDA about “promising results” in third-line metastatic colorectal cancer, Arcus said the companies decided to forgo a phase 3 trial for the A2a/A2b receptor antagonist and that Gilead has handed back its license.

Gilead is still hoping to reap rewards from its bet on Arcus through other candidates in the deal, including a late-stage drug targeting TIGIT, an approach that’s shown some promise but has also been beset by disappointing results.

Gilead and Arcus believe their anti-TIGIT drug domvanalimab could have an edge in the space due to its unique formulation. The companies are testing the treatment in combination with chemotherapy and an investigational PD-1 inhibitor, and expect initial phase 3 results next year.

China has rapidly emerged as a global force in oncology, contributing a significant share of next-generation immunotherapies to the cancer pipeline, including a standout candidate that could rival Merck & Co.’s megablockbuster Keytruda. 

Chinese drugs account for 51% of antibody-drug conjugates in development, 48% of bispecific monoclonal antibodies and 48% of CAR-T therapies, according to Mark Lansdell, director of custom intelligence at Evaluate. 

Western drugmakers have taken notice of the country’s advances and dealmaking is booming. In 2023 and 2024, approximately 30% of molecules in-licensed by Big Pharma companies came from China, Lansdell said. The agreements include major deals by companies such as Merck and Novartis. 

“That’s up from 0% just six years prior,” he noted. 

Upcoming U.S. trial results for ivonescimab, developed by Chinese biopharma Akeso and licensed by U.S.-based Summit Therapeutics, may mark a pivotal moment for China’s trajectory in oncology. 

The drug, already approved in China, is a bispecific antibody that targets both PD-1 and vascular endothelial growth factor (VEGF), a protein that promotes blood vessel growth and helps shield tumors from the immune system. It significantly outperformed Keytruda in a head-to-head phase 3 Chinese trial for non-small cell lung cancer, nearly doubling progression-free survival. Overall survival, however, did not show a statistically significant improvement because the data were immature and there were not enough patients in the study to draw firm conclusions. 

Keytruda, a PD-1 inhibitor, has redefined treatment standards across several cancers, and if U.S. trials, including one with an anticipated December 2025 completion date, confirm the result of Chinese trials, it could provide a big boost to the country’s oncology efforts, Lansdell said. The drug’s potential has already sparked a flurry of deals as companies look to license their own checkpoint inhibitors that also target VEGF. 

“If results don’t replicate, I think that will have a dampening effect,” Lansdell said. 

An emerging force

Chinese firms have evolved from their earlier role as support staff for Western pharma companies. In the late 1990s and early 2000s, pharmas began enlisting Chinese companies to carry out some of the more mundane aspects of drug development while retaining control over molecule design and biological pathway selection, Lansdell said. 

“It was only a matter of time before those skilled [Chinese] scientists started to think, ‘Why don't we start our own drug discovery business rather than always acting as a service for Western companies?’” he said.

Most Chinese companies aren’t pursuing game-changing innovations but are primarily focused on improving or adapting existing drug approaches.

“Given enough time, my expectation is that China will start to explore novel biology and get better at discovering new ways to target diseases,” Lansdell said. “And that will be an interesting challenge for the West.”

U.S. companies are increasingly recognizing the value of licensing drugs from China, where trials are cheaper and get started more quickly due to the country’s faster enrollment rates. 

“Seventy-five percent of all China-developed companies are in clinical trials, while in the U.S. only 64% of companies are in the clinic,” Lansdell said. 

China’s drug regulator, the National Medical Products Administration, is a member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, so companies follow internationally standardized human clinical trials practices, Lansdell said. But the FDA remains cautious of single-country trials and prefers broader validation. While data from Chinese trials alone may not have been enough to get a nod from the FDA in the past, mindsets are changing, and they can give pharma companies the confidence to proceed with a deal.

Predicting future growth

Chinese companies without a commercial footprint outside the country have an incentive to make deals. Without U.S.-based partners it’s difficult to break into the global market. While many experts anticipated a further acceleration of 2024’s record-breaking deal making with Chinese companies, Lansdell said this year’s data shows it’s holding steady. 

“The momentum we saw in 2024 has been sustained, but not built upon,” Lansdell said.

It’s not clear if Chinese drug developers will continue to focus on Western markets or pivot to the domestic market, according to Lansdell.

“I think you are going to see more companies decide to develop drugs for their domestic market,” he said. “The excitement about being able to out-license to Western companies will dampen over time because it will reach a saturation point.”

Other questions remain about China’s trajectory. 

“Will they take that next step and start innovating on the biology side? How long will it take? What happens when they start to do that?” Lansdell said.

Antibody-drug conjugates were the topic du jour at this year’s annual meeting of the American Society of Clinical Oncology and the rising trend in cancer care has many in the industry champing at the bit for a piece of the action.

It wasn’t always a sure bet that ADCs would break through the noise, though. The first one approved by the FDA — Mylotarg from Pfizer subsidiary Wyeth for acute leukemia — came to market in 2000. The company voluntarily withdrew the treatment 10 years later due to high liver toxicity, but the concept was strong. 

A cancer-killing drug with an antibody homing device attached has the potential to target specific tumors and keep dosing to a healthier minimum. 

“It’s essentially smart chemo,” said Ethan Smith, therapy area director for oncology at Norstella.

Despite a rough start, researchers have been tearing down the walls in subsequent generations of ADCs. Now, 15 different molecules have been approved by the FDA. The latest, Emrelis from AbbVie, represents a distinct approach to non-small cell lung cancer by targeting the biomarker c-Met.

The scientific and market success of flagship ADCs like Daiichi Sankyo and AstraZeneca’s groundbreaking breast, gastric and lung cancer drug Enhertu is paving the way for the modality to move into earlier lines of therapy for patients, as well as the next generation of targeted cancer medicines.

Being the ‘flag carrier’

While drugmakers have overcome some of the early safety challenges of ADCs, getting the formula to the right balance of cancer-killing effectiveness without dangerous side effects is still tricky.

“One of the biggest challenges of ADCs that hasn’t really gone away is engineering them — you’ve got your [monoclonal antibody], your linker and your payload, and making sure they all work in tandem has been difficult,” Smith said. “It’s only been around the last five years where many of these challenges have been resolved.”

Getting the drug-to-antibody ratio correct and a stabilized linker to deliver a potent payload without too many off-target effects has been the goal for drug developers. And the established target of HER2, present in about one in five instances of breast cancer, helped make Enhertu an important entry, Smith said.

“For most analysts, Enhertu has the highest forecasted revenues and is the one breaking a lot of ground, particularly across breast cancer in nearly every setting,” Smith said. “It is a flag carrier of ADCs.”

One of the compelling aspects of ADCs is you can rechallenge a target, Smith said. For example, a patient taking Roche’s monoclonal antibody Herceptin for a HER2-positive tumor can follow up with Enhertu afterward without encountering resistance to the target — only resistance to the payload, which is another hurdle moving forward.

Enhertu is also proving its worth in earlier stages of care. At ASCO, one of the most talked-about studies was a late-stage trial in which the treatment outperformed chemotherapy as a first-line drug.

Smith called it potentially “practice changing.”

Daiichi Sankyo is now seeking approvals in these earlier-disease positions, Ken Keller, head of the company’s global oncology business unit, said during a PharmaVoice and BioPharma Dive event this year.

“As successful as Enhertu has been so far, the story is still evolving,” Keller said. “Most of our indications early on were in late-stage disease patients who had failed many lines of therapy — we’re at the point in its life now where we have top-line readouts for a number of different studies that are moving Enhertu earlier and earlier in the treatment paradigm.”

And like many roads in oncology, Enhertu’s leads to tie-ups with other successful cancer treatments to squeeze as much utility out of the molecule as possible.

“As we move earlier, almost all of our trials will be in combination with different [immuno-oncology] drugs and … even chemotherapy drugs,” Keller said. “As you move forward, the opportunity to leverage different [mechanisms of action], especially ADCs and IO therapies, that’s going to deliver the best outcomes for patients.”

Pfizer rising

This year’s ASCO meeting has had the biggest ADC showing to date, which has been growing year by year, Smith said.

“Back when ADCs first came into play, that was before we had a lot of the validated targets we have today,” Smith said. “HER2 has been around for a long time and remains an established target, but now we’re seeing much bigger development in the payloads themselves for a next generation of ADCs.”

For example, Pfizer, which acquired early ADC innovator Seagen in 2023, is going after a familiar target in the oncology arena: the PD-(L)1 pathway. Checkpoint inhibitors like Merck & Co.’s Keytruda and Bristol Myers Squibb’s Opdivo, among many others, have blocked the pathway in an immuno-oncology setting, and Pfizer is betting the same tracking mechanism can help an ADC shine.

Pfizer has also teamed up with biotech Summit Therapeutics to combine ADCs with bispecific antibodies in early-stage development.

“There’s not much detail on it, but if that’s something that’s successful, they could be riding not just an ADC wave but the PD-(L)1 and VEGF wave with Summit,” Smith said. “That’s something to look out for.”

Gilead’s Trodelvy also turned heads at ASCO with a study in first-line triple-negative breast cancer along with Keytruda. Providing a chemo-free treatment as a first option for patients would address a highly unmet-need population, Smith said.

Leading a trend

Being an early adopter of an oncology trend like ADCs isn’t always an easy feat to pull off for drugmakers. While data is king, getting a foot in the door requires a first step into the unknown, Smith said.

“The proof in these trends is always the data, but companies can’t wait that long — the later someone is to a licensing deal, the more they have to pay,” Smith said. “In truth, a lot of these licensing deals happen on faith, and perhaps some desperation.”

And the industry doesn’t always move on the right trends. A rush on Lag3 blockades, for instance, brought on the approval of Bristol Myers Squibb’s melanoma drug Opdualag in 2022, but a series of trial failures and axed programs from pharma giants like Merck and Roche left a sour taste.

Even though it takes faith to enter the arena, data will still always be the true test of a modality’s lasting power, Smith said.

“A trend is only confirmed when you’ve got that threshold of data — even if you see a bunch of companies licensing a new technology, that doesn’t validate it,” Smith said. “Perhaps it’s just pessimism, but until you have that validated data, it’s best to stay away from the noise of licensing activity.”

ADCs are beginning to cross that threshold, he said. Between established leaders and a slate of novel targets on the way, some hurdles remain, but the trend is shaping up to be a game changer.