WU-NK-101

P1, N=9, Active, not recruiting, Wugen, Inc. | Recruiting --> Active, not recruiting | N=24 --> 9

P1, N=24, Recruiting, Wugen, Inc. | Trial primary completion date: Apr 2024 --> Dec 2024

The resulting "Prime and Expand" ML NK cells exhibited elevated metabolic capacity, stable epigenetic IFNG promoter demethylation, enhanced antitumor activity in vitro and in vivo, and superior persistence in NSG mice. Thus, the "Prime and Expand" strategy represents a simple feeder cell-free approach to streamline manufacturing of clinical-grade ML NK cells to support multidose and off-the-shelf ACT.

P1, N=30, Recruiting, Wugen, Inc. | Not yet recruiting --> Recruiting | Trial primary completion date: Feb 2025 --> Sep 2025

P1, N=30, Not yet recruiting, Wugen, Inc. | Phase classification: P1b --> P1 | Initiation date: Nov 2023 --> Jun 2024

Patients were lymphodepleted with fludarabine and cyclophosphamide...Multi-modal analyses of WU-NK-101 highlight unique transcriptional and functional states, which could underpin in vivo potency and persistence. WU-NK-101 are currently being evaluated in a phase 1 study of R/R AML (#NCT05470140).

Overall, W-NK inherently survives and maintains function in the TME, a limiting factor for immune cell-based ACT. These data herald the promise of NK cell therapy; a Phase 1 clinical study of W-NK in acute myeloid leukemia is currently open and enrolling patients (NCT# 05470140).

P1, N=24, Recruiting, Wugen, Inc. | Not yet recruiting --> Recruiting

P1b, N=30, Not yet recruiting, Wugen, Inc. | Initiation date: May 2023 --> Nov 2023

Patients will receive a lymphodepleting chemotherapy regimen (cyclophosphamide 50 mg/kg and fludarabine 125mg/kg) starting on days -6 to -2 prior to receiving WU-NK-101... Response assessment will take place on Day 28 (+/-3 days), by bone marrow aspirate and core biopsy, and response will be defined per 2022 European LeukemiaNet criteria. Response rate, duration of response, and mortality rate at 1 and 3 months will be evaluated. Clinical trial, Cellular therapy, NK cell, Acute myeloid leukemia

ML-NK cell infusion was associated with TME modulation and engagement of the endogenous adaptive immune response. The high T-cell infiltration to the tumor site post-treatment points to the recruitment of the adaptive immune system and signals the potential for durable effectiveness. A phase 1 study of WU-NK-101 in R/R AML is in development (#NCT05470140).

P1, N=24, Not yet recruiting, Wugen, Inc. | Initiation date: Mar 2023 --> Jul 2023

In summary, WU-NK-101 has the potential to reverse primary and acquired mechanisms of ICB resistance. A Phase 1b clinical trial of WU-NK-101 as salvage therapy post-ICB is in development.

P1b, N=30, Not yet recruiting, Wugen, Inc.

P1, N=24, Not yet recruiting, Wugen, Inc. | Initiation date: Dec 2022 --> Mar 2023

Successive cohorts of 3 to 6 patients will be enrolled using a standard 3 + 3 design.Once the maximum tolerated/administered dose is defined, 6 additional patients will be enrolled in the Cohort Expansion Phase to further characterize the safety, tolerability, as well as determine the recommended Phase 2 dose of WU-NK-101.Patients will receive a lymphodepleting chemotherapy regimen (cyclophosphamide 50mg/kg and fludarabine 125mg/kg) starting on days -6 to -2 prior to receiving WU-NK-101...Key exclusions are circulating blast count >30,000/µL by morphology or flow cytometry (cytoreductive therapies such as leukapheresis or hydroxyurea are allowed); uncontrolled or untreated bacterial or viral infections; uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG suggestive of acute ischemia or active conduction system abnormalities; and severe renal impairment.Response assessment will take place on Day 28 (+/-3 days), by bone marrow aspirate and core biopsy, and response will be defined per 2022 European LeukemiaNet criteria. Response rate, duration of response, and mortality rate at 1 and 3 months will be evaluated.

Cytokine-induced memory-like (CIML) NK cells are more potent for anti-tumor responses than conventional NK (cNK) cells, are well tolerated, and active in patients with R/R AML (NCT#01898793) with complete response (CR)/CR with partial/incomplete hematologic recovery rate of 47% and a median DOR of 9.4 months after a single infusion (Berrien-Elliott, et al...Compared to cNK cells, WU-NK-101 had enhanced trafficking to the BM, anti-tumor activity, and a metabolic profile consistent with aerobic glycolysis, potentially contributing to mitigating TME adversity. Due to their resilience to an immunosuppressive TME, WU-NK-101 cells may represent an effective treatment modality for R/R AML; a phase 1 study of WU-NK-101 in R/R AML is in development (NCT #05470140).

P1, N=24, Not yet recruiting, Wugen, Inc.