Merck and Daiichi Pulled an ADC Filing as GSK Paid $110 Million for a KRAS Payload
The antibody-drug conjugate field is splitting in two. Crowded designs built on topoisomerase I payloads now face a regulator that wants randomised evidence, while the money moves to new payload mechanisms, two-target antibodies and the discovery tools behind them. Almost every asset on the moving side was invented in China.
Daiichi Sankyo and Merck withdrew their US application for ifinatamab deruxtecan, a B7-H3 ADC with a topoisomerase I payload, in previously treated extensive-stage small cell lung cancer, saying the current dataset did not support approval. The filing had breakthrough designation and priority review. It shows how far single-arm data can carry an ADC in a crowded class: as far as priority review, and not to approval.
In the same month, two conjugates carrying RAS inhibitors instead of cytotoxins moved within five days of each other. GSK paid HUTCHMED $110 million upfront for HMPL-A830, a KRAS inhibitor linked to an anti-EGFR antibody, and Adlai Nortye dosed the first patient with AN4035, a CEACAM5 antibody carrying a pan-RAS(ON) inhibitor, after FDA clearance.
Bispecific ADCs are the other growth lane. Iza-bren, an EGFR x HER3 bispecific partnered with Bristol Myers Squibb, won its first approval in China in June and has three positive Phase 3 trials, and Alphamab licensed its TROP2 x HER3 bispecific JSKN016 to Pathos in August for $125 million upfront.
Large companies are also selling the ADCs they no longer want to fund and paying for tools that pick the next ones. Pfizer licensed a former Seagen ADC to Medicus for $12 million upfront, WuXi XDC licensed its exatecan payload-linker for the second time this year, and Daiichi Sankyo extended Turbine’s virtual biology platform across its ADC programmes.
The FDA drew a line under single-arm data for a crowded ADC class
Daiichi Sankyo and Merck said on 25 September that their Biologics License Application for ifinatamab deruxtecan, in adults with extensive-stage small cell lung cancer progressing on or after platinum chemotherapy, had been voluntarily withdrawn. The application sought accelerated approval, had priority review from April 2026 and followed a breakthrough therapy designation in August 2025. Marjorie Green, Merck’s head of oncology clinical development, said the current dataset did not support approval at this time.
Ifinatamab deruxtecan pairs a B7-H3 antibody with DXd, a topoisomerase I inhibitor from the same payload family as Enhertu and Datroway. Phase 3 trials continue in castration-resistant prostate cancer and oesophageal squamous cell carcinoma, and the companies say they are still evaluating the drug in small cell lung cancer.
The read-across reaches every company with a B7-H3 or DLL3 conjugate in small cell lung cancer. A drug with breakthrough status, priority review and a top-tier sponsor could not convert single-arm data into an accelerated approval, so competitors should budget for randomised evidence before filing. That favours sponsors with the balance sheet for Phase 3 and penalises those whose plan rests on an early US filing.
Two RAS-inhibitor conjugates entered the race within five days
On 3 September HUTCHMED licensed HMPL-A830 to GSK outside Greater China for $110 million upfront and up to $1.295 billion in total, plus royalties. The conjugate links a selective KRAS inhibitor to an anti-EGFR antibody for colorectal, pancreatic and lung cancers. HUTCHMED runs the global Phase 1, due to start in the second half of 2026, and closing awaits antitrust review.
Five days later Adlai Nortye reported FDA clearance and its first patient dosed in Australia for AN4035, which carries a pan-RAS(ON) inhibitor on a CEACAM5 antibody aimed at the same three tumour types. The company describes it as the first pan-RAS(ON) ADC in the clinic and argues that systemic pan-RAS inhibitors are held back by skin and gastrointestinal toxicity that targeted delivery could avoid. Initial clinical data are expected in 2027.
| HMPL-A830 | AN4035 | |
|---|---|---|
| Developer | HUTCHMED; GSK holds rights outside Greater China | Adlai Nortye; no licence disclosed |
| Antibody target | EGFR | CEACAM5 |
| Payload | Selective KRAS inhibitor | Pan-RAS(ON) inhibitor |
| Lead tumours | Colorectal, pancreatic, lung | Colorectal, pancreatic, lung |
| Stage | Global Phase 1 due to start in the second half of 2026 | Phase 1 dosing; FDA clearance in September 2026 |
| Combination | Not disclosed | Cetuximab arm alongside monotherapy |
| Economics | $110m upfront; up to $1.295bn in total | Not applicable |
| Next marker | First patient dosed | Initial clinical data in 2027 |
Both programmes use the payload as a targeted drug, and both point it at RAS-driven colorectal, pancreatic and lung cancer, where systemic RAS inhibitors are advancing in parallel. Adlai Nortye’s own framing is the strategic point: today’s ADC payloads sit almost entirely in two classes, topoisomerase I and microtubule inhibitors, so resistance to one ADC can carry over to the next. A new payload class is a route around that cross-resistance, and GSK has now paid to own one.
Bispecific ADCs reached approval in China and a $2.2 billion licence in the West
Iza-bren, the EGFR x HER3 bispecific ADC from Sichuan Biokin and SystImmune, was approved in China in June for recurrent or metastatic nasopharyngeal carcinoma after platinum and PD-(L)1 therapy, on a confirmed response rate of 54.6% against 27.0% for chemotherapy. Interim Phase 3 analyses have since shown overall and progression-free survival gains in triple-negative breast cancer and oesophageal squamous cell carcinoma. Bristol Myers Squibb co-develops the drug outside China, where it holds US breakthrough designation in EGFR-mutated lung cancer.
On 3 August Alphamab licensed JSKN016, a TROP2 x HER3 bispecific ADC in Phase 3 for triple-negative breast cancer in China, to Pathos outside Greater China for $125 million upfront and up to about $2.09 billion in milestones, with royalties from high single to low double digits.
Both assets were designed in China and licensed out before Western registration data existed, the same structure as HMPL-A830. For Western developers, the benchmark for a two-target design is now a Chinese Phase 3 dataset, and JSKN016’s $125 million upfront sets a reference price for licensing one.
| Asset | Originator | Licensee | Territory | Upfront | Headline value |
|---|---|---|---|---|---|
| HMPL-A830 | HUTCHMED, China | GSK | Outside Greater China | $110m | Up to $1.295bn |
| JSKN016 | Alphamab, China | Pathos | Outside Greater China | $125m | About $2.2bn |
| CD228V | Pfizer, from Seagen | Medicus Pharma | Worldwide | $12m, plus $15m in 2027 | Over $1bn in milestones |
| WuXiTecan-2 | WuXi XDC, China | Ona Therapeutics | Worldwide, one target | Undisclosed | Undisclosed |
The flow runs in two directions. Chinese originators are licensing new mechanisms west at upfronts of $110 million to $125 million, while a US major hands a discontinued asset to a small company for $12 million and keeps the upside through milestones and an option to fund pivotal development.
Pfizer is pruning Seagen’s pipeline and keeping an option on what it lets go
Medicus Pharma licensed PF-08046031, or CD228V, an early clinical-stage ADC against melanotransferrin that Pfizer acquired with Seagen and stopped developing. Medicus paid $12 million on 2 September and owes $15 million on the first anniversary, while Pfizer pays Medicus $2 million in development funding, keeps the patents and can fund development once a pivotal trial begins. Milestones exceed $1 billion, with low double-digit royalties.
The structure gives Pfizer cheap optionality: a small partner carries the cost of early development, and Pfizer can step back in once the data justify a pivotal trial. Expect more of the same as large companies that bought ADC platforms decide which programmes still earn internal funding.
The discovery layer is becoming a product of its own
WuXi XDC granted Ona Therapeutics an exclusive global licence on 17 September to its exatecan-based WuXiTecan-2 payload-linker for one undisclosed target, with an upfront payment, milestones and royalties, and with WuXi XDC handling manufacturing. It is the platform’s second out-licence of 2026, after a multi-target agreement with Earendil Labs in February.
On 24 September Daiichi Sankyo expanded its collaboration with Turbine after a feasibility programme, applying Turbine’s vLab virtual assays across its proprietary ADC programmes to reduce wet-lab experimentation. Turbine began a similar ADC collaboration in October 2025 with AstraZeneca, Daiichi Sankyo’s partner on Enhertu and Datroway.
Payload-linker chemistry and experimental triage are now licensed as standalone products. That lowers the entry cost for small developers and means topoisomerase I payloads, the most crowded class, are also the easiest to rent, so differentiation moves to targets, formats and the payload mechanisms no platform yet sells off the shelf.
The ADC field is sorting into a crowded lane and a moving one
Set side by side, the month’s moves describe where the pressure is building and where capital is going.
Where the bar is rising
- Single-arm accelerated filings in crowded classes, as the ifinatamab deruxtecan withdrawal shows
- Topoisomerase I payloads, now available to rent from platform licensors
- Early programmes in large portfolios that no longer earn internal funding
Where the money is moving
- Payloads that are targeted drugs, led by KRAS and pan-RAS inhibitors
- Bispecific ADCs with Phase 3 data generated in China
- Discovery tools that cut wet-lab work, sold to the companies with the largest ADC portfolios
The hardest position belongs to Western developers with a single-target topoisomerase I ADC in a crowded class. They face a higher regulatory bar, chemistry their competitors can license, and Chinese rivals with two-target designs already in Phase 3.
What to watch
Closing of the GSK and HUTCHMED agreement after antitrust review, and the first patient in HMPL-A830’s global Phase 1, due in the second half of this year.
AN4035’s dose-escalation safety in 2027, the test of whether an ADC can deliver pan-RAS inhibition without the skin and gastrointestinal toxicity that limits systemic drugs.
Bristol Myers Squibb’s registration plan for iza-bren outside China, which would put a Chinese-designed bispecific ADC into Western pivotal trials.
And the Phase 3 readouts for ifinatamab deruxtecan in prostate and oesophageal cancer, which now carry the asset’s US prospects.
The coverage will log another China licensing deal. The signal that matters is the payload: a field that has relied largely on two mechanisms is now paying for a third.