The First Granzyme B Radiopharmaceutical Platform

Our platform leverages granzyme B (GzmB) as a functional biomarker, which is only released when T cells and NK cells are actively engaging and killing tumor cells. This unique feature allows us to map exactly which tumors or parts of tumors the immune system is attacking.

Unlike static markers such as PD-L1 staining or CD8 counts, which only indicate the potential for immune activity, granzyme B provides proof of ongoing cell killing.^{[IV]Comparisons to other biomarkers. PD-L1/CD8 reflects presence/phenotype; GzmB indicates functional cytotoxic activity. Modalities can be complementary; context determines utility.} By homing in on active granzyme B, we ensure that our diagnostic and therapeutic agents are exceptionally precise. This accuracy is crucial: it provides our radiodiagnostic with the accurate data needed to predict if a therapy is working^{[III]Predictive/diagnostic performance. Any “predict/predictive,” “sensitivity/specificity,” or “trial acceleration/early readout” language reflects ongoing evaluation; figures from early-phase or limited cohorts may change in later studies.} and ensures our radioimmunotherapy only targets the tumor itself—with minimal harm to healthy tissue.^{[II]Mechanism & selectivity limits. “Targeted immune stimulation,” “spares healthy tissue,” “precision-guided,” and “feed-forward/overcoming exhaustion” describe intended mechanisms supported primarily by preclinical or dosimetry work. Actual selectivity depends on biodistribution, dose, timing, and patient biology; absence of off-target effects is not guaranteed.}

Granzyme B (GzmB) provides a platform that is tumor-agnostic because it targets the immune system’s activity rather than a specific antigen on a tumor. Therefore, our radiodiagnostic, CSB-321, can identify sites of granzyme B release across all cancer types, including primary tumors and metastases, regardless of their genetic makeup or phenotype.^{[V]Tumor-agnostic & heterogeneity. “Tumor-agnostic” derives from targeting immune activity (GzmB) rather than tumor antigens; detection requires immune killing to be present or inducible. Not all tumors/regions will generate a measurable GzmB signal.}

Unlike traditional antigen-locked approaches—which are designed to target cancer cell-specific protein and can fail when that target is absent or becomes heterogeneous due to therapeutic pressure—our platform adapts. Since granzyme B is a universal marker of active killing that is “painted” onto tumors, it effectively reduces the chance of tumor escape by bypassing the need for a cancer cell-based target.^{[V]Tumor-agnostic & heterogeneity. “Tumor-agnostic” derives from targeting immune activity (GzmB) rather than tumor antigens; detection requires immune killing to be present or inducible. Not all tumors/regions will generate a measurable GzmB signal.} The benefit is a more robust and reliable tool for a broader range of cancers, providing accurate data even when tumors are complex and diverse.

The Granzyme B (GzmB) biomarker offers a level of exquisite precision because effector cells release it only at the exact site where immune cells are actively killing tumor cells. This highly localized signal ensures that our imaging and therapeutic agents are directed only to the “kill spot,” bypassing healthy tissue.^{[II]Mechanism & selectivity limits. “Targeted immune stimulation,” “spares healthy tissue,” “precision-guided,” and “feed-forward/overcoming exhaustion” describe intended mechanisms supported primarily by preclinical or dosimetry work. Actual selectivity depends on biodistribution, dose, timing, and patient biology; absence of off-target effects is not guaranteed.}

Unlike other methods that target broad, nonspecific antigens present on both cancerous and healthy cells, our approach focuses on functional, real-time immune activity. The benefit is a highly targeted and effective therapy that minimizes off-target effects and potential harm to healthy cells, significantly improving the safety profile for patients.^{[II]Mechanism & selectivity limits. “Targeted immune stimulation,” “spares healthy tissue,” “precision-guided,” and “feed-forward/overcoming exhaustion” describe intended mechanisms supported primarily by preclinical or dosimetry work. Actual selectivity depends on biodistribution, dose, timing, and patient biology; absence of off-target effects is not guaranteed.} This precision also enables more accurate diagnostic insights, as we are only detecting genuine immune-mediated cell death.

Our platform’s ability to measure Granzyme B (GzmB) activity makes it the ideal companion for combination therapies. The feature is our ability to detect immune activity induced by a variety of drugs and treatment modalities, from immunotherapies to chemotherapy. This function enables us to monitor and quantify the combined effect of different treatments^{[VI]Combination therapy variability. GzmB signals from multi-agent regimens vary by drug, sequence, dose, and timing; monitoring combinations remains an investigational approach.} working together to kill cancer cells in real-time.^{[I]Timing & “real-time.” “~14-day” and “real-time” refer to common imaging timepoints under study (discrete scans), not continuous monitoring. Actual schedules, performance, and interpretation vary by protocol/indication.}

Unlike approaches that can only track a single drug’s effect on a specific target, our platform provides a unified view of the entire immune response. The benefit is a more comprehensive picture of how a combination therapy is performing, enabling doctors and researchers to identify the most effective drug pairings quickly. Early readouts lead to more successful treatment outcomes^{[III]Predictive/diagnostic performance. Any “predict/predictive,” “sensitivity/specificity,” or “trial acceleration/early readout” language reflects ongoing evaluation; figures from early-phase or limited cohorts may change in later studies.} and accelerate the development of potent new therapeutic combinations.^{[VI]Combination therapy variability. GzmB signals from multi-agent regimens vary by drug, sequence, dose, and timing; monitoring combinations remains an investigational approach.}