An Antibody-Drug Conjugate (ADC) has created the first breakthrough in the osteosarcoma market, which had gone more than 40 years without a new drug. The ADC "Risledez," developed by China's Hansoh Pharma with global rights secured by the United Kingdom's GSK, demonstrated efficacy for the first time in a phase 3 trial in osteosarcoma.
The industry is watching to see whether ADCs can take hold as a new therapy in osteosarcoma on the back of these results. Attention is also turning to "SOT106," an ADC candidate in development by Czech company Sotio Biotech for the same indication. SOT106 applies Sotio's Antibody-Drug Conjugate (ADC) platform "ConjuALL" to Sotio's antibody and LigaChem Biosciences(141080).
◇ First phase 3 success for an osteosarcoma ADC…a signal of change in a long new-drug drought
On Aug. 28 (local time), GSK released results from "ARTEMIS-011," a phase 3 osteosarcoma trial of Risledez conducted in China by Hansoh Pharma.
In this study of osteosarcoma patients whose disease progressed or recurred after at least two lines of systemic chemotherapy, Risledez significantly prolonged progression-free survival (PFS) versus standard chemotherapy. It also showed a consistent trend of improvement in secondary endpoints, including overall survival (OS), and no new safety issues were identified.
Hansoh Pharma plans to seek marketing approval in China based on these results. However, detailed data such as the median PFS, hazard ratio (HR), and p-value have not yet been disclosed.
Osteosarcoma is the most common primary malignant tumor originating in bone and occurs mainly in children and young adults. While the patient population is small, it is a representative rare cancer in which treatment options drop sharply upon relapse. There is currently no approved therapy for patients whose disease has progressed after two or more lines of treatment.
Osteosarcoma has also been a cancer type where ADC development repeatedly hit a wall. ABBV-085, an ADC developed by U.S.-based AbbVie targeting LRRC15, showed about a 20% objective response rate (ORR) in osteosarcoma, signaling potential, but development was halted after it failed to deliver expected results in other solid tumors.
Leveraging its global rights outside China, GSK is conducting global phase 1b/2 studies in sarcoma patients, including osteosarcoma, while pursuing a multi-tumor development strategy to expand indications to lung and prostate cancers.
◇ Same target, different strategy…a proving ground for "SOT106" differentiation
Following GSK's success, competition in osteosarcoma ADC development appears to be picking up again. Among the latecomers drawing attention is Sotio's SOT106. SOT106 targets the same LRRC15 as AbbVie's earlier ABBV-085, but its drug design is different.
Sotio concluded that the limitations of ABBV-085 lay not in the target itself but in the design of the antibody, linker, and payload that make up the ADC. It therefore newly designed the candidate by applying LigaChem Biosciences' ConjuALL platform to its own antibody. ConjuALL is designed to keep the antibody and cytotoxic drug stable in the bloodstream and release the payload only after entering cancer cells.
It also uses MMAE, a microtubule inhibitor payload, and increases the drug-to-antibody ratio (DAR) from two in ABBV-085 to four. The strategy is to boost both the amount of drug delivered to cancer cells and delivery efficiency, even while aiming at the same target.
Preclinical results suggested these design changes could translate into safety. In a good laboratory practice (GLP) toxicology study in monkeys, SOT106 showed a highest non-severely toxic dose (HNSTD) of 9 mg/kg without severe toxicity. ABBV-085's was 3 mg/kg.
Radek Spisek, Sotio's chief executive officer (CEO), recently said at "LigaChem Biosciences Global R&D Day 2026," "Taking the DAR difference into account, the practical therapeutic safety margin is about 18 times wider than the prior candidate." In other words, there is more leeway to administer more drug relatively safely while achieving the same therapeutic effect.
Efficacy also improved. In an osteosarcoma xenograft animal model, SOT106 showed superior antitumor activity compared with the standard chemotherapy doxorubicin and ABBV-085. In repeat experiments, it also reproduced complete disappearance of tumors to the point of being undetectable on imaging.
A LigaChem Biosciences official said, "While B7-H3, the target of Risledez, aims at a range of solid tumors, LRRC15, the target of SOT106, tends to have higher expression specificity in sarcomas including osteosarcoma," adding, "We expect competitiveness in terms of both efficacy and safety."
◇ FDA orphan designation…first patient dosing within the year
In June, the U.S. Food and Drug Administration (FDA) designated SOT106 as an orphan drug (ODD) and granted fast track (expedited review) for the osteosarcoma indication. Sotio plans to submit an investigational new drug (IND) application and clinical trial application (CTA) at the end of this month or in September in Moldova, where regulatory procedures are relatively fast, and begin first patient dosing within the year.
The clinical design also seeks to differentiate from prior candidates. Sotio plans to enroll only patients with an LRRC15-positive cell ratio of 1% or higher. Using its in-house diagnostic kit, the strategy is to first select patients more likely to have the drug correctly recognize the target. Unlike AbbVie, the company aims to verify from early-stage trials the link between target expression and treatment effect.
LigaChem Biosciences expects this patient-selection strategy to raise the chances of early clinical success. A company official said, "Preselecting patients who respond well allows us to assess key endpoints more clearly," adding, "Regulators have recently been encouraging biomarker-based patient selection."
The market size is not small even considering this is a rare cancer. In the United States and Europe, about 36,000 soft tissue sarcoma patients and about 8,000 osteosarcoma patients are newly diagnosed each year. CEO Spisek estimated SOT106's potential market at more than 10,000 patients annually. Applying only a conservative assumption that 3,500 of them receive treatment for an average of six months, annual sales of $700 million to $800 million (about 1 trillion won) could be achievable.
If clinical potential is confirmed in osteosarcoma, Sotio plans to expand development to other solid tumors with the same target. LRRC15 is known to be expressed not only in osteosarcoma but also in some breast and head and neck cancers.
If SOT106 demonstrates differentiated safety and efficacy in clinical trials, sublicensing talks could also gain momentum. CEO Spisek left the door open to partnerships, saying, "We plan to conduct phase 1 on our own, but because sarcoma is a rare disease with many subtypes, it is efficient to develop it with a global pharmaceutical company that has experience."
A sublicense is a contract in which a company that received a technology license transfers development and sales rights to a third party. If a deal is struck, LigaChem Biosciences, which provided the original platform technology, could also receive additional milestones and sales royalties depending on the deal structure.
A LigaChem Biosciences official said, "It is meaningful that GSK confirmed the potential of ADCs in osteosarcoma, but there is still room to further improve outcomes," adding, "SOT106 will maintain a strategy focused not on speed but on achieving best-in-class status by improving both efficacy and safety."