Y-mAbs Presents Translational Pharmacokinetics of CD38-SADA From Pretargeted RIT Platform

Y-mAbs Therapeutics, Inc. recently announced the presentation of preclinical and translational pharmacokinetics (PK) data of CD38-SADA in a poster at the 2025 American Association of Cancer Research (AACR) Annual Meeting being held on April 25-30, 2025 in Chicago, IL.

The poster titled Preclinical and translational pharmacokinetic (PK) modeling of the self-assembling and disassembling (SADA) bispecific fusion protein CD38-SADA for first-in-human (FIH) pretargeted radioimmunotherapy (PRIT) characterizes the plasma concentrations of CD38-SADA in animal models over time and a range of doses. Utilizing in vitro binding kinetic parameters and PK data generated from three studies in mice, the study characterized the concentration- and time-dependent equilibrium between CD38-SADA tetramers and monomers.

Previous preclinical reports have shown that the non-radiolabeled CD38-SADA tetramers bind with high-avidity to tumors during the first “pre-targeting” infusion. Building on these data, the preclinical PK model tracked the plasma levels of the CD38-SADA protein. Importantly, the model’s estimated linear clearance of low molecular weight CD38-SADA monomers was 20-times faster than the CD38-SADA tetramers, providing additional evidence for their significantly reduced levels before delivery of the radioactive payload in the second infusion. This is an important consideration in evaluating the tumor-to-normal tissue absorbed dose ratios of Lutetium 177 (Lu 177)-DOTA, the chelated radionuclide administered in Trial 1201.

“Our preclinical models have provided important insights into the circulating levels of CD38-SADA protein in vivo,” said Brian Santich, Ph.D., lead author and Vice President of Research. “Using these data, we conducted a series of appropriately scaled human PK simulations which informed the design and initial dosing regimen of our first-in-human Phase 1 Trial 1201 in patients with r/r NHL.”

“With the recent dosing of our first patient in Trial 1201, we look forward to reviewing initial patient data as our CD38-SADA program advances,” said Norman LaFrance, MD, co-author and Chief Medical and Development Officer.

Researchers at Memorial Sloan Kettering Cancer Center (MSK), including Dr. Nai-Kong Cheung, developed the SADA technology for radioimmunotherapy, which is exclusively licensed by MSK to Y-mAbs. Dr. Cheung has intellectual property rights and interests in the technology, and as a result of this licensing arrangement, MSK has institutional financial interests in the technology.

Y-mAbs is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, radioimmunotherapy and antibody-based therapeutic cancer products. The Company’s technologies include its investigational Self-Assembly DisAssembly (SADA) Pretargeted Radioimmunotherapy Platform (PRIT) and bispecific antibodies generated using the Y-BiClone platform. The Company’s broad and advanced product pipeline includes the anti-GD2 therapy DANYELZA (naxitamab-gqgk), the first FDA-approved treatment for patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow after a partial response, minor response, or stable disease to prior therapy.

CD38-SADA is a bispecific fusion protein that tightly binds to the CD38 glycoprotein and to ¹⁷⁷Lu-tetraxetan (¹⁷⁷Lu -DOTA), a “caged” radionuclide. In the first step of pre-targeted radioimmunotherapy, non-radiolabeled CD38-SADA tetramers are infused and bind to CD38-expressing lymphoma cells, and unbound CD38-SADA protein disassembles into low molecular weight monomers that are removed by the kidney. The second infusion delivers the “radioactive payload,” which binds directly to CD38-SADA on tumor cells for localized irradiation. CD38-SADA PRIT with ¹⁷⁷Lu-DOTA has demonstrated robust anti-tumor efficacy in preclinical studies and is currently being investigated in adults with relapsed, progressive, or refractory NHL (CD38-expressing B-cell, T-cell, and natural killer cell lymphomas) after at least 2 prior lines of therapy (NCT05994157).