Hutchmed China has announced that its subsidiary, Hutchmed Limited, has entered into an exclusive development and license agreement with a subsidiary of GSK plc, granting the GSK subsidiary worldwide rights excluding Mainland China, Hong Kong, Macau and Taiwan to develop and commercialise HMPL-A830. 

Clinical development will initially focus on colorectal, pancreatic and lung cancer indications. The agreement includes a USD 110 million upfront payment and potential development, regulatory and commercial milestone payments, for up to a total of USD 1.295 billion, and royalties on net sales. This first-in-class drug candidate, an ATTC, comprises a highly selective and potent Kirsten Rat Sarcoma (KRAS) small molecule inhibitor payload conjugated to an anti-Epidermal Growth Factor Receptor (EGFR) antibody. An antibody-targeted therapy conjugate enables tumour-selective activity of potent, cell-killing payloads by leveraging antibody-guided therapy.

Colorectal, lung and pancreatic cancers have the highest incidence of patients with KRAS-altered tumours, who often lack a safe and durable KRAS therapy. HMPL-A830 is designed to address this need by delivering a KRAS inhibitor directly to EGFR-expressing tumours, while simultaneously blocking EGFR and KRAS signalling to enhance efficacy, durability and tolerability. This exclusive license for HMPL-A830 is a first-in-class KRAS-EGFR ATTC, which is expected to enter clinical trials in H2 2026.

Under the terms of the agreement, Hutchmed Limited will be responsible for the global phase I development programme, which is expected to start in the second half of 2026. The GSK subsidiary will be responsible for all subsequent clinical development and commercialisation activities outside of Mainland China, Hong Kong, Macau and Taiwan.

Johnny Cheng, Acting CEO and CFO of Hutchmed, said, “We are proud to work with GSK, a globally leading biopharmaceutical company that, like Hutchmed, is committed to developing innovative new cancer medicines to address significant unmet medical needs worldwide. Our ATTCs combine antibodies with our proprietary small-molecule inhibitor payloads to deliver dual mechanisms of action. HMPL-A830 is our third drug candidate from these novel payload platforms and the first from our platform to be licensed to a global partner, following two candidates that have entered clinical development. This collaboration marks a significant step in maximizing its potential as a treatment for patients, unlocking an entirely new class of precision oncology medicines.”

Dr Hesham Abdullah, senior VP, global head oncology, R&D, GSK, said, “This agreement reflects GSK’s growing leadership across oncology and our commitment to advance the latest innovation for patients living with cancer. The dual KRAS-EGFR mechanism of HMPL-A830 has the potential to significantly improve upon current standard of care. We look forward to working with Hutchmed to progress this innovative asset through development.”

Under the agreement, Hutchmed Limited will receive an upfront payment of USD 110 million and may receive additional development, regulatory and commercial milestone payments of up to a total of USD 1.185 billion. The GSK subsidiary GSK Intellectual Property will also pay tiered royalties on its annual net sales. Hutchmed will retain full development and commercialisation rights in Mainland China, Hong Kong, Macau and Taiwan. In addition, the GSK subsidiary has a right of first negotiation on one earlier stage ATTC drug candidate. The upfront payment is payable at closing, which is subject to customary closing conditions, including completion of any antitrust regulatory reviews.

Hutchmed's ATTCs represent a next-generation approach to precision oncology, combining monoclonal antibodies with proprietary small-molecule inhibitor payload platforms to deliver dual mechanisms of action. Unlike traditional cytotoxin-based antibody-drug conjugates, ATTCs combine targeted therapies to achieve synergistic anti-tumour activity and durable responses in preclinical models, outperforming standalone antibody or small-molecule inhibitor components in both efficacy and safety.

RAS mutations represent one of the most prevalent and well-established drivers in human oncology, driving the progression and aggressive pathology of multiple solid tumours. KRAS, the most dominant RAS isoform, is mutated in approximately 44 percent of colorectal cancer, 34 percent of lung adenocarcinoma and up to 89 percent of pancreatic ductal adenocarcinoma patients. 

While recent targeted therapies have validated KRAS as a viable therapeutic target, significant clinical gaps persist, particularly for patients with non-G12C mutations. Most patients eventually experience disease progression driven by acquired resistance, largely fuelled by upstream receptor tyrosine kinase upregulation and secondary KRAS alterations. Beyond mutation coverage, systemic delivery of pan-KRAS and pan-RAS inhibitors is associated with on-target toxicities, such as dermatological toxicity reflecting RAS pathway inhibition in normal tissue. These present challenges for dosing, long-term tolerability, and combination with cytotoxic chemotherapy or immunotherapy backbones that constitute frontline standard-of-care.

EGFR has also emerged as a key mediator of resistance to KRAS-targeted therapies, particularly in CRC, where adaptive feedback and increased upstream EGFR signalling reactivate the MAPK pathway and limit the depth and durability of KRAS inhibition. Together, these provide a strong rationale for the dual targeting of EGFR and KRAS, not only in CRC but also additional indications such as PDAC and NSCLC.