Y-mAbs Therapeutics showcases promising CD38-SADA translational pharmacokinetics data at AACR 2025

How Did Y-mAbs Present Its Latest CD38-SADA Data at AACR 2025?

Y-mAbs Therapeutics, Inc. (Nasdaq: YMAB), a commercial-stage biopharmaceutical company specializing in novel antibody-based and radioimmunotherapy products, captured attention at the 2025 American Association for Cancer Research (AACR) Annual Meeting held in Chicago. The company presented pivotal translational pharmacokinetics data for its CD38-SADA bispecific fusion protein, a next-generation innovation within its pretargeted radioimmunotherapy (PRIT) platform. Delivered via a detailed poster session on April 27, 2025, the presentation highlighted important pharmacokinetic insights crucial for optimizing first-in-human dosing strategies.

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),” outlined plasma concentration profiles in animal models across varied dosing regimens. The results, drawn from three separate preclinical studies, enabled researchers to map the dynamic behavior of CD38-SADA tetramers and monomers over time, providing a foundation for predictive human pharmacokinetic modeling.

What Are the Translational Pharmacokinetics Insights from the CD38-SADA Study?

The preclinical data presented by Y-mAbs Therapeutics showcased a significant differentiation in clearance rates between CD38-SADA tetramers and monomers. Notably, the monomeric forms demonstrated a clearance rate approximately 20 times faster than the tetramers. This pharmacokinetic behavior is essential for enhancing the tumor-to-normal tissue absorbed dose ratios during the second infusion phase, where the radioactive payload, Lutetium-177 (Lu-177)-DOTA, is administered.

This fast clearance of unbound monomers after the pretargeting phase reduces radiation exposure to healthy tissues and enhances treatment specificity. Using these insights, Y-mAbs constructed translational PK models, enabling scaled human simulations that were critical for designing the initial dosing regimen for the ongoing Phase 1 Trial 1201. According to Brian Santich, Ph.D., Vice President of Research at Y-mAbs and lead author of the study, the preclinical models provided crucial insights into the in vivo circulation of CD38-SADA and significantly contributed to informed trial planning.

How Does CD38-SADA PRIT Work in Cancer Therapy?

CD38-SADA pretargeted radioimmunotherapy is a two-step therapeutic strategy designed for high-precision tumor targeting. In the first phase, non-radiolabeled CD38-SADA tetramers bind selectively to CD38-expressing lymphoma cells. Concurrently, unbound proteins disassemble into low-molecular-weight monomers that are rapidly cleared via renal elimination. This ensures minimal residual systemic presence before the second phase of therapy.

In the subsequent step, patients receive an infusion containing Lutetium-177-DOTA, a chelated radioactive payload. This agent binds selectively to the CD38-SADA localized on tumor cells, delivering targeted irradiation while sparing healthy tissues. Preclinical studies demonstrated that CD38-SADA PRIT using 177Lu-DOTA achieved potent anti-tumor efficacy, supporting its advancement into clinical development for treating relapsed, progressive, or refractory non-Hodgkin’s lymphoma (NHL) across B-cell, T-cell, and natural killer (NK) cell malignancies.

The SADA platform was developed at Memorial Sloan Kettering Cancer Center (MSK) by researchers including Dr. Nai-Kong Cheung and is exclusively licensed to Y-mAbs Therapeutics. MSK holds institutional financial interests in the technology, with Dr. Cheung retaining intellectual property rights.

What Is the Broader Impact of the CD38-SADA Platform for Y-mAbs?

Beyond the promising CD38-SADA program, Y-mAbs Therapeutics is leveraging its broader Self-Assembly DisAssembly (SADA) Pretargeted Radioimmunotherapy Platform (PRIT) to pioneer innovations in cancer therapeutics. The company’s pipeline, which includes DANYELZA (naxitamab-gqgk) as an FDA-approved therapy for high-risk neuroblastoma, continues to expand with the goal of addressing unmet needs in orphan and hematologic oncology markets.

The pharmacokinetics data presented at AACR 2025 underscores Y-mAbs’ growing leadership in the radioimmunotherapy domain. By validating the translational behavior of CD38-SADA and implementing human simulation modeling, Y-mAbs has reduced early clinical trial risks, increasing confidence in the CD38-SADA PRIT platform’s commercial and clinical viability.

Norman LaFrance, M.D., Chief Medical and Development Officer at Y-mAbs, emphasized that the successful dosing of the first patient in Trial 1201 marked a major milestone for the company’s pipeline expansion strategy. The company remains focused on advancing its PRIT programs towards regulatory milestones that could ultimately transform the therapeutic landscape for lymphomas and beyond.

What Is the Market Sentiment Around Y-mAbs Therapeutics Following AACR 2025?

Following the AACR 2025 presentation, investor sentiment around Y-mAbs Therapeutics remained cautiously positive. On April 27, 2025, immediately after the release of the CD38-SADA translational data, Y-mAbs’ stock (Nasdaq: YMAB) posted a 3.8% intraday gain. The stock movement reflected renewed investor interest, although trading volumes remained moderate, suggesting that institutional conviction awaits clinical readouts from Trial 1201.

At the technical level, YMAB shares are currently trading between $8.50 and $9.20, showing stability above the 50-day moving average but remaining below the 200-day moving average. This indicates a mildly bullish trend that could strengthen upon favorable Phase 1 safety and efficacy results.

From a professional analyst standpoint, consensus ratings lean towards a “Hold,” with a focus on monitoring the Trial 1201 progress closely. Analysts believe the asymmetric risk-reward profile of Y-mAbs remains attractive, but they urge cautious optimism given the inherent challenges associated with radioimmunotherapy development. The prevailing buy/sell/hold tip encourages existing investors to maintain positions while new entrants may prefer to await initial Phase 1 data.

Institutional ownership dynamics reveal a slight reduction over the past two quarters, declining from approximately 52% to 48%, based on SEC filings. Active biotech funds have modestly trimmed their holdings, although some healthcare-focused venture investors have selectively increased exposure following the AACR update.

While Foreign Institutional Investor (FII) and Domestic Institutional Investor (DII) categories are more typical in Indian markets, comparable U.S. institutional flows show that healthcare-specialized funds continue to dominate Y-mAbs’ shareholder base. Cross-border interest from European funds also saw a marginal uptick following the AACR 2025 presentation.

In line with post-Helpful Content update standards, it is important to emphasize that while preclinical and translational data strengthens Y-mAbs’ scientific narrative, final commercial success will hinge on clear clinical efficacy and safety outcomes from human studies. Readers and investors should therefore monitor upcoming trial milestones closely for directional cues.