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The next wave of ADC value will come from engineering, not new targets
For antibody-drug conjugates (ADCs), a validated target no longer sets a program apart: sponsors are betting the next wave of value will come from chemistry and engineering that widen the therapeutic window, not from new target biology. Sleuth’s August 2026 analysis counts 23 ADC programs approved worldwide, about 50 in Phase 3 and about 440 in the clinic, out of roughly 2,045 programs tracked across all statuses. ADCs are now a mature modality, but the first generation exposed its limits: narrow therapeutic windows that force dose reductions in combination, and resistance to the dominant payload classes, including TOP1 mutations that blunt topoisomerase-1 payloads.
The engineering bets are new payload mechanisms, linker and conjugation design, and bispecific or dual-payload constructs. A wider window gives an ADC room to dose higher, combine at full strength and revisit targets and treatment settings that first-generation constructs could not make work. Buyers are already paying for those bets before clinical proof, as Gilead’s agreement to acquire Tubulis for up to $5 billion and Novartis’s up-to-$1.5 billion acquisition of payload developer Myricx Bio showed in 2026.
About 440 of roughly 2,045 ADC programs have reached the clinic
Most of the pipeline is preclinical, and few developers have real depth
Of the roughly 2,045 ADC programs in Sleuth’s all-status universe, 1,562 (76%) are preclinical and 42 are at IND. About 440 have reached Phase 1 or later: 188 in Phase 1, 124 in Phase 1/2, 43 in Phase 2, 52 in Phase 3, 8 filed and 23 approved. The 1,838 active programs span 313 targets.
Developer depth is thinner than the program count suggests. Of about 640 active ADC developers, only 59 meet a multi-program test, such as running clinical programs across two or more payload classes or repeatedly out-licensing ADCs, and 33 of those lead with an approved or Phase 3 asset. For buyers, the set of proven platform builders is small, and competition for them is correspondingly intense.
Target crowding pushes differentiation into payload, linker and conjugation
HER2, EGFR, TROP2, B7-H3, c-Met and HER3 each have more than 20 clinical-stage ADC programs. Past a basic level of validation, clinical counts stop scaling with interest: HER2 has about 160 active programs but only 35 in the clinic, close to B7-H3 (24 of 80) and c-Met (24 of 74). Sleuth also found 75 unique bispecific ADC target pairs, led by EGFR plus c-Met, with 40 in the clinic and 4 in Phase 3.
A validated target is now table stakes. Because the payload, linker, conjugation method and drug-to-antibody ratio each change how an ADC behaves, sponsors can build a differentiated asset against a crowded antigen, and there is less pressure to chase new biology. What separates two HER2 ADCs is the construct, not the target name.
Payload chemistry is consolidating, which makes new warheads scarce
Among the roughly 110 clinical-stage programs that disclose a payload, auristatins and topoisomerase-1 inhibitors (including DXd) account for about 44%. MMAE leads individual classes with 18 programs, followed by exatecan and DM4 with 14 each, and topoisomerase-1 has overtaken MMAE as the most contested warhead to license. About 75% of clinical ADC programs do not disclose their payload, and protein-degrader payloads have only one or two clinical programs. The companion ADC payload landscape groups all tubulin inhibitors with topoisomerase-1 across every development stage, which is why it finds about 86% of disclosed payloads in those two mechanism groups.
When the core chemistry commoditizes and resistance to TOP1 payloads emerges, a differentiated warhead becomes the scarce asset. That explains why Novartis paid for Myricx’s N-myristoyltransferase inhibitor payloads before any product reached the market, and why buyers are paying platform prices for preclinical payload chemistry.
The therapeutic window decides how far an ADC can go
Dose caps limit what an ADC can add in combination
Sleuth mapped 166 ADC combination pairings. Checkpoint and other immuno-oncology partners account for 73 (44%), chemotherapy and backbone agents for 40 (24%) and targeted agents for 21 (13%). Pairing with a checkpoint inhibitor is the default and adds little differentiation on its own.
Dose intensity matters more. Trastuzumab deruxtecan, sacituzumab govitecan and datopotamab deruxtecan, the three most-combined ADCs, all carry explicit dose constraints, so their combinations run at reduced intensity and give back some of the efficacy the partner was meant to add. ADCs with a wider window can stack with standard therapy at full dose, which is why Sleuth is watching wider-window designs such as Sutro’s STRO-004.
First-line entry usually depends on combining at full dose
Owning a first-line indication is the main value trigger, because frontline use drives disproportionate volume. Entry is rare and usually follows approval in later lines. Enfortumab vedotin plus pembrolizumab set the benchmark in urothelial cancer, with median progression-free survival of 12.5 months against 6.3 months in EV-302, and in 2026 two TROP2 ADCs, datopotamab deruxtecan and sacituzumab govitecan, won first-line approvals in metastatic triple-negative breast cancer.
Most first-line entries have come in combination with standard of care, including enfortumab vedotin with pembrolizumab, polatuzumab vedotin with R-CHP and brentuximab vedotin with AVD, so frontline conversion usually requires stacking at full dose. The 2026 TNBC approvals include monotherapy for patients who cannot receive PD-(L)1 inhibitors, which shows an ADC can also win first line alone where standard options are weak. Developers and buyers should underwrite the migration path, not just the entry indication. The path is not guaranteed: in second-line NSCLC, every ADC that tested overall survival in an unselected population has failed.
Buyers are paying for ADC platforms before clinical proof
Deal count nearly doubled from 2021 to 2025
Sleuth tracked 393 ADC deals announced from 2021 through August 2026. Annual deal count rose from 49 in 2021 to 93 in 2025, and the 48 deals through August 2026 put the year on pace for about 70. Disclosed value is lumpy: $51.2 billion in 2023 included the $22 billion Daiichi Sankyo and Merck deal, and upfronts were a thin slice of headline value, about $1.8 billion of $41.5 billion in 2025.
Of the 303 deals with a known stage at signing, 219 (about 72%) were preclinical. Buyers do not need clinical data to place a bet. What they need is evidence that a payload or conjugation platform, if validated, could be applied broadly across targets. With 70 or more deals a year and modest upfronts, waiting for proof is likely to cost buyers more than acting early. The independent payload developers still available are mapped in Sleuth’s novel ADC payload landscape.
Dual-payload and bispecific designs move the combination inside the molecule
Sleuth’s dual and next-generation ADC landscape covers 106 programs: 42 dual-target or bispecific ADCs, 13 ADC-plus-inhibitor designs and 11 dual-payload ADCs. About 86% are preclinical. China originates 62 (58%), with 14 in the clinic, while none of the 20 US programs has reached the clinic. Only 4 of the 106 belong to big pharma: Pfizer, Lilly, AstraZeneca and Novartis.
The leading dual-payload pairs couple a topoisomerase-1 warhead with a second payload that blocks the DNA damage response, such as an ATR inhibitor or an RNA polymerase II inhibitor, and preclinical models show regression where each payload alone failed. Because combination efficacy is capped by the dose window, putting both mechanisms in one molecule lets one window cover both. Lilly paid up to $300 million for CrossBridge Bio before the clinic, but upcoming Phase 1 safety readouts will decide whether these designs widen the usable window or simply add toxicity.
China originates half of the global ADC pipeline
China leads Phase 3, while ex-China developers lead approvals
China originates about 1,045 of the roughly 2,045 ADC programs (51%). It leads the combined rest of the world in Phase 3, 32 programs to 20, and runs 739 preclinical programs against 427 in the US. Developers outside China still lead in approvals, 13 to 10. China’s structural advantage concentrates where medicinal chemistry and development speed matter most, and ADCs are the clearest example of the pattern in Sleuth’s China biopharma landscape.
That Phase 3 cohort can go two ways: a large late-stage partnering wave for Western buyers, or a new era of China-originated ADCs launched globally by their developers.
China has become a standing sourcing channel for ADCs
Of 150 mapped China-origin ADC deals, 59 were domestic and about 87 were out-licensed, with the US the largest destination at 44 deals and Europe at 26. Scale alone does not signal quality. Biocytogen, for example, runs about 30 programs with one in the clinic, while MediLink, CSPC, Biokin, Kelun and DualityBio combine clinical depth with repeat partnering or late-stage validation.
For pharma, China is a sourcing channel to track continuously rather than one deal at a time. For biotechs, it is both a partner map and a competitor set. About 60% of China-to-global ADC deals are WuXi-enabled, a supply-chain concentration buyers should diligence as the BIOSECURE Act is implemented.
The near-term openings are in TROP2, B7-H3 and non-oncology
HER2 catalysts extend leaders, while TROP2 can reset the order
Sleuth tracked 51 active Phase 3 or pivotal ADC programs. HER2 anchors the late-stage calendar, but its events are mostly label expansions for established franchises such as Enhertu, which compound the incumbents’ lead. TROP2 is the live opening, mixing label expansions with first approvals. Emerging targets with pivotal-stage programs include DLL3 (Zai Lab’s ZL-1310), CDH6 (Daiichi Sankyo and Merck’s raludotatug deruxtecan) and B7-H4 (AstraZeneca’s AZD8205).
In B7-H3, only a differentiated construct still has room
The B7-H3 field has at least 80 active ADC programs, and 15 of the 26 named clinical competitors are China-based. At the August 2026 snapshot, Daiichi Sankyo and Merck’s ifinatamab deruxtecan (I-DXd) led on regulatory speed, with a US application under Priority Review in previously treated extensive-stage small-cell lung cancer on a 48.2% response rate. On September 25, 2026, the companies withdrew that application after the FDA said the Phase 2 data did not meet the bar for accelerated approval, and a new filing now depends on the Phase 3 IDeate-Lung02 trial.
I-DXd’s lead came from regulatory timing rather than exclusive biology, and that lead has narrowed. A straight DXd copy still faces a leader with a pivotal trial well under way and several other B7-H3 ADCs, mostly from China, in Phase 3 or filed. The defensible entry is a construct the leader cannot simply out-file, such as a bispecific or a non-DXd payload, for example IDEAYA’s B7-H3 x PTK7 bispecific IDE034.
Beyond oncology, ADCs become a payload-innovation story
Sleuth counted 39 non-oncology antibody-conjugate programs with enough evidence to classify. Autoimmune and immunology is the largest area with 15 programs, followed by infectious disease with 10. Here the payload is no longer cytotoxic: DB-2304 pairs an anti-BDCA2 antibody with a glucocorticoid for lupus, and the only Phase 3 program, del-desiran, is an antibody-oligonucleotide conjugate for myotonic dystrophy type 1 that missed its primary functional endpoint in the HARBOR trial in September 2026. AbbVie’s two anti-TNF ADCs reached Phase 2 before being discontinued. Unlike oncology, sponsors here are mostly North American.
The design problem shifts from killing tumor cells to delivering a mechanism, such as a steroid or an siRNA, to specific cells where it would be too toxic or too diffuse given systemically. The field is early, but the platform logic that made dual payloads bankable before proof applies here too.
What the ADC findings mean for developers and buyers
These implications are Sleuth’s interpretation of the data above.
For ADC developers, the construct is the position. In a crowded target, a construct that holds its dose in combination is worth more than a new antigen. Build the platform case early by showing the payload or conjugation chemistry could work across several targets, because that is what buyers pay for before clinical data. Plan the route to first line from the start, since it usually runs through full-dose combination with standard of care.
For buyers and BD teams, waiting is expensive. With about 70 or more ADC deals a year, most signed preclinically, the price of proof keeps rising. Diligence should focus on therapeutic index and dose intensity in combination rather than target novelty, and on supply-chain exposure for China-originated assets. China’s deep developers deserve continuous tracking, not a look after each headline deal.
What Sleuth expects next in ADCs
These predictions are Sleuth’s analytical interpretation, looking beyond what the data shows today.
- A dual-payload platform will trade for more than $1 billion in headline value. Lilly paid up to $300 million for CrossBridge before the clinic, and once Phase 1 safety readouts clear, the next platform will reset multiples.
- Non-oncology will become the next pre-proof platform bet, following the same pattern as dual payloads, with platform chemistry attracting acquisitions before clinical readouts.
- The biggest buyouts will reward therapeutic index, not novel targets. The most successful next-generation ADCs will deliver the therapeutic index that first-generation ADCs failed to achieve against the same targets. Tubulis, with its NaPi2b ADC, is the reference point for this model.
How Sleuth built this analysis
Pipeline and targets
The full ADC universe covers about 2,045 programs across all statuses, including discontinued and inactive programs. The active subset of 1,838 programs spans 313 targets. Multi-target drugs count in every target they address, so target counts sum to more than the total. Clinical stage means Phase 1 or later.
Developers
Sleuth counted about 640 active ADC developers. A developer is multi-program if it has two or more clinical programs across two or more payload classes, a multi-target clinical portfolio or repeat ADC out-licensing.
Payloads
Payload shares cover at least 110 clinical-stage programs across 22 payload classes, with one primary payload class per drug. Programs that do not disclose a payload are excluded rather than counted as zero.
Deals
The deal set covers 393 ADC deals announced from January 2021 through August 2026. Dollar figures are disclosed value only, and disclosure varies by year. Stage at signing is known for 303 deals. The China deal map is a subset of 150 deals with known origin and destination, and likely an undercount.
Combinations and next-generation designs
Combination figures count 166 pairings rather than programs. Dose signals draw on 24 Project Optimus dose-optimization instances. The dual and next-generation landscape covers 106 programs, and first-line milestones are a curated set of approvals, pivotal readouts and filings from 2021 to 2026.
Non-oncology and interpretation
The non-oncology count covers 39 programs, from 43 audited less 4 with insufficient evidence. Antibody-oligonucleotide conjugates are shown for context and are not added to oncology counts. The implications and predictions are Sleuth’s analytical interpretation rather than direct findings from the data.
Pipeline, deal and clinical figures are as of August 2026 unless otherwise noted. Regulatory updates after the snapshot are current as of September 2026.
Frequently asked questions about the ADC landscape
How large is the global ADC pipeline?
Sleuth tracked about 2,045 antibody-drug conjugate programs across all statuses as of August 2026. The active subset of 1,838 programs spans 313 targets, and about 440 programs have reached Phase 1 or later.
How many antibody-drug conjugates are approved?
Sleuth counted 23 approved ADC programs worldwide as of August 2026, 13 originating outside China and 10 in China. Another 8 were filed and 52 were in Phase 3.
Which ADC targets are the most crowded?
HER2, EGFR, TROP2, B7-H3, c-Met and HER3 each have more than 20 clinical-stage ADC programs. HER2 has the most active programs, about 160, but only 35 are in the clinic.
Which payloads dominate clinical ADC development?
Auristatins and topoisomerase-1 inhibitors, including DXd, account for about 44% of the roughly 110 clinical-stage ADC programs that disclose a payload. About 75% of clinical programs do not disclose their payload.
Why does the therapeutic window matter for an ADC?
The therapeutic window sets how much drug a patient can receive before toxicity limits the dose. A wider window lets an ADC combine with standard therapy at full dose, which most first-line ADC approvals have required.
What is a dual-payload ADC?
A dual-payload ADC carries two payloads with different mechanisms on one antibody. Leading designs pair a topoisomerase-1 warhead with a second payload that blocks DNA damage repair, so one therapeutic window covers both mechanisms. Sleuth counted 11 dual-payload ADCs within a 106-program next-generation landscape, most still preclinical.
How much of the ADC pipeline comes from China?
China originates about 1,045 of the roughly 2,045 ADC programs, or 51%. It leads the rest of the world in Phase 3 programs, 32 to 20, while developers outside China lead in approvals, 13 to 10.
How often are ADC deals signed before clinical data?
About 72% of ADC deals with a known stage at signing (219 of 303) were preclinical, within 393 ADC deals Sleuth tracked from 2021 through August 2026. Buyers are paying for platforms they expect to apply across multiple targets.
What is the status of I-DXd, the leading B7-H3 ADC?
Daiichi Sankyo and Merck withdrew their US application for ifinatamab deruxtecan in previously treated extensive-stage small-cell lung cancer on September 25, 2026, after the FDA said the Phase 2 data did not support accelerated approval. A future filing depends on the Phase 3 IDeate-Lung02 trial.
