[Edaily Reporter KIM SAE-MI ] LigaChem Biosciences(141080)(141080)’s receptor tyrosine kinase-like orphan receptor 1 (ROR1)-targeted antibody-drug conjugate (ADC) “LCB71” achieved complete remission (CR) in all 31 patients in a combination clinical trial for the first-line treatment of diffuse large B-cell lymphoma (DLBCL). The partner company temporarily suspended the trial to evaluate long-term benefits and risks and to optimize the dosage and administration schedule.

LigaChem Biosciences announced on the 28th that updated results from the Phase 1b clinical trial of “CS5001 (LCB71)” were disclosed in the first-half financial results released by its partner, CStone Pharmaceuticals, on the 27th.

Based on an August cutoff this year, in a study of first-line DLBCL patients treated with the combination of CS5001 and the standard therapy R-CHOP, the objective response rate (ORR) among 31 evaluable patients at doses ranging from 40 to 90 μg/kg was 100% (31 patients), and the complete remission (CR) rate was also 100% (31 patients). All patients who responded achieved a complete remission (CR); none achieved only a partial response (PR).

By dose group, all patients achieved CR: 8 at 40 μg/kg, 12 at 50 μg/kg, 8 at 70 μg/kg, and 3 at 90 μg/kg. Notably, this update included data for the first time on the 8 patients in the lowest dose group (40 μg/kg), which had not been previously disclosed. All of these patients also achieved CR.

Compared to the data released last March, the number of patients evaluated increased by 9, from 22 to 31, and the CR rate rose from 95.5% (21 patients) to 100%. At that time, in the 50 μg/kg group, 10 out of 11 patients achieved CR and 1 achieved PR; however, in the August cutoff, all 12 patients were assessed as having achieved CR. The CR rates for the 70 μg/kg and 90 μg/kg groups remained at 100%, consistent with previous results.

LigaChem Biosciences is noting that a 100% CR rate was observed even at the lowest dose of 40 μg/kg. The company explains that since a 100% CR rate was consistently observed across all dose groups—from 40 μg/kg to 90 μg/kg, despite a more than twofold difference in dose—it is possible to explore reducing the dosage to improve tolerability while maintaining efficacy in the future. The company believes these results will serve as a basis for evaluating the therapeutic window of CS5001 and determining the optimal dose.

Siston has currently temporarily suspended the CS5001 clinical trial. Siston explained that this is to evaluate existing clinical data from the perspective of long-term benefits and risks and to optimize the dosage and administration schedule.

LigaChem Biosciences distinguishes this temporary suspension from the termination of clinical development. The company explains that the status “Suspended” on clinical trial registration sites indicates that patient enrollment or drug administration has been halted prematurely but may resume in the future, and is distinct from “Terminated,” which signifies that the trial has been permanently ended. The company believes that, given the high response rate observed even at the lowest dose, it has now entered a phase where it can reevaluate the appropriate dose and dosing schedule based on the accumulated efficacy and safety data.

CS5001 is an ROR1-targeted ADC jointly developed by LigaChem Biosciences and ABL Bio Inc. It incorporates LigaChem Biosciences’ tumor-selective cleavable linker and pyrolobenzodiazepine (PBD) prodrug payload into ABL Bio Inc.’s ROR1 antibody. Cyston’s materials also highlight the tumor-selective cleavable linker and the PBD prodrug as key design features of CS5001.

In 2020, LigaChem Biosciences transferred the global development and commercialization rights for CS5001 (excluding Korea) to Cyston. The deal comprised an upfront payment of $10 million (approximately 13.9 billion KRW), milestone payments totaling up to $353.5 million (approximately 490 billion KRW), and separate royalties.

The company expects that the accumulation of clinical data for CS5001 in the future will also influence the potential for sublicensing. LigaChem Biosciences’ technology transfer agreement is structured such that, if a partner company sublicenses a candidate compound it has acquired to a third party, LigaChem Biosciences is entitled to receive a share of the upfront payment, milestones, and royalties in accordance with the terms of the agreement.

LigaChem Biosciences currently views CS5001, as well as “LCB14 (IKS014),” “LCB73 (IKS03),” and “IKS04,” as partner development assets with potential for future sublicensing. A LigaChem Biosciences official stated, “When Big Pharma conducts due diligence, they place significant importance not only on the response rate but also on the dose at which the response was observed,” adding, “Since a high response rate has been confirmed even at low doses, this is significant in terms of the potential to improve tolerability through dose optimization or to expand combination therapy options in the future.”