WU-NK-101 / Wugen, HCW Biologics - LARVOL DELTA

Cytokine Induced Memory-like NK Cell Adoptive Therapy for Relapsed AML After Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: Washington University School of Medicine | Active, not recruiting ➔ Recruiting | N=62 ➔ 110 | Trial completion date: Nov 2025 ➔ Oct 2028 | Trial primary completion date: Nov 2025 ➔ Oct 2028

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Transplantation

Cytokine Induced Memory-like NK Cell Adoptive Therapy for Relapsed AML After Allogeneic Hematopoietic Cell Transplant (clinicaltrials.gov) - P1/2 | N=62 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting | N=110 ➔ 62 | Trial completion date: Oct 2028 ➔ Nov 2025 | Trial primary completion date: Oct 2028 ➔ Nov 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Transplantation

A Phase 1b Study of WU-NK-101 in Combination With Cetuximab (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Wugen, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • EGFR

WUN101-01: First in Human Human (FIH) Phase 1 Study of WU-NK-101 (W-NK1) in Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (ASH 2024) - P1 | "Cytokine Release Syndrome was reported in 4 (44.4%) pts, all G1, typically occurring the day of first or second infusion, a median duration of 2 days, and managed to complete resolution with antipyretics +/- tocilizumab...Overall, W-NK1 has demonstrated a tolerable and manageable safety profile with preliminary evidence of anti-tumor activity. Furthermore, our study highlights the evolution, expansion, and persistence of W-NK1 in patients with AML, suggesting W-NK1 as a best-in-class NK cell therapy."

Clinical • P1 data • Acute Myelogenous Leukemia • Anemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • CX3CR1 • CXCR3 • IL2 • NCAM1

W-NK1 Choreographs Innate and Adaptive Immune Responses to Provide a Robust and Durable Anti-AML Response (ASH 2024) - "In this manner the pharmacodynamic effect of W-NK1 extends far beyond the pharmacokinetic effect. These data augur positively for patients to be treated with W-NK1 in future studies."

IO biomarker • Acute Myelogenous Leukemia • Oncology • CCL2 • CCL20 • CD40 • CD80 • CD83 • CD86 • CXCL10 • CXCL11 • CXCL9 • IFNG • IL2RA • KLRC1 • SEMA4D • TNFA

Wugen to Present Clinical Data at the 2024 ASH Annual Meeting… (GlobeNewswire) - "Researchers will present Phase 1/2 updates and studies for its investigational cell therapies this week...'At this year’s ASH meeting, we will present clinical data from adult and adolescent patients that support our soon to open pivotal trial for patients with relapsed or refractory T-ALL/LBL'...The pivotal Phase 2 study is a single-arm trial evaluating the efficacy and safety of WU-CART-007 in patients with R/R T-ALL/LBL and T-ALL/LBL...Wugen researchers will also present the following abstracts for the company’s investigational memory natural killer cell therapy, WU-NK-101"

Clinical data • Acute Myelogenous Leukemia • T Acute Lymphoblastic Leukemia

WUN101-01: A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Wugen, Inc. | Trial completion date: Dec 2025 ➔ Jan 2025

Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

WU-NK-101 conditions the tumor microenvironment (TME) by engaging with the innate and adaptive immune system resulting in a robust and durable anti-tumor response (SITC 2024) - "Ethics Approval This study involving the use of mice adheres to international, national, and institutional guidelines for the humane treatment of animals and complies with relevant legislation. The research protocol has been reviewed and approved by the Charles River Ethics Review Committee at the Gradlabs vivarium facility (San Diego, CA) where the studies were conducted."

Biomarker • Tumor microenvironment • Oncology • Solid Tumor • IL2RA

HCW Biologics Reports Second Quarter 2024 Financial Results and Business Highlights (GlobeNewswire) - "Business Highlights...Going forward, the Company retains ownership and control of the TOBI platform and TOBI-based molecules, with no restrictions under the Settlement Agreement on its ability to use the TOBI platform for protein-fusion molecules for non-oncology indications. The Company may pursue the clinical development of treatments for cancer indications based on HCW9302, HCW9206 and HCW9201. Further, HCW Biologics retains ownership of the Wugen license and shares of Wugen common stock transferred to the Company as the upfront licensing fee from Wugen for granting the Wugen license...R&D expenses for the quarter ended June 30, 2023 and 2024 were $1.6 million and $2.0 million, respectively...Manufacturing costs increased in three- and six-month periods ended June 30, 2024 because the Company was replenishing its supply of a high-expressing cell line of HCW9101."

Commercial • Licensing / partnership • Hematological Malignancies • Immunology • Oncology • Solid Tumor

WUN101-01: A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Wugen, Inc. | Recruiting ➔ Active, not recruiting | N=24 ➔ 9

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

WUN101-01: A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Wugen, Inc. | Trial primary completion date: Apr 2024 ➔ Dec 2024

Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

A "Prime and Expand" strategy using the multifunctional fusion proteins to generate memory-like NK cells for cell therapy. (PubMed, Cancer Immunol Immunother) - "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."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • IFNG • IL12A • IL15 • IL18 • IL21 • IL7

A Phase 1b Study of WU-NK-101 in Combination With Cetuximab (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Wugen, Inc. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Feb 2025 ➔ Sep 2025

Combination therapy • Enrollment open • Metastases • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • EGFR

WU-NK-101 IS AN OFF-THE-SHELF MEMORY NK CELL WITH A TME-RESILIENT, ANTI-TUMOR PHENOTYPE THAT CAN BE DETECTED IN R/R AML PATIENT PBMC AFTER INFUSION (EHA 2024) - "We show that W-NK1 displays a robust memory NK phenotype and expression ofmolecules we hypothesize could enhance their fitness in a metabolically hostile tumor microenvironment. Importantly, this advantageous W-NK1 phenotype can be clearly observed in the PBMC of R/R AML patientsafter therapeutic transfer (NCT# 05470140). Future studies will reveal how the W-NK1 phenotype is altered inpatient PBMC over time and whether attributes of W-NK1 phenotype are associated with response totreatment."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Oncology • B3GAT1 • CD2 • CD86 • IL2RA • NCAM1 • NKG2D • TFRC

WU-NK-101 (W-NK), a Memory-like (ML) NK Cell, Naturally Overcomes Tumor Microenvironment (TME) Metabolic Challenges, Retaining Anti-Tumor Potency (ASH 2023) - "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)."

Biomarker • Tumor microenvironment • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • SLC1A5 • SLC2A1 • SLC3A2 • SLC7A5 • TGFB1

Adoptively Infused Memory-like Natural Killer Cells Impact Adaptive Immune Responses in Patients with Acute Myeloid Leukemia (ASH 2023) - P1 | "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)."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • CD276 • CD34 • CD7 • CD8 • HAVCR2 • IL12A • IL15 • IL18 • LAG3 • NCAM1 • PARP1 • STING • TRB

WU-NK-101 (W-NK), a Memory-like (ML) NK Cell, Intrinsically Overcomes Factors Restricting Adoptive Cell Therapy (ACT) in Acute Myeloid Leukemia (AML) (ASH 2023) - "Moreover, they are not restricted to a single antigen target thereby mitigating antigen escape. These features, which overcome challenges for ACT, herald the promise of NK cell therapy and augur positively for patients being treated with W-NK in a Phase 1 study in R/R AML (NCT# 05470140)."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • CXCR4 • GLUL • GZMB • IL12A • IL15 • IL2 • NKG2D • TGFB1 • TXNIP

A Phase 1b Study of WU-NK-101 in Combination With Cetuximab (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Wugen, Inc. | Phase classification: P1b ➔ P1 | Initiation date: Nov 2023 ➔ Jun 2024

Combination therapy • Metastases • Phase classification • Trial initiation date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • EGFR

WU-NK-101, an off-the-shelf memory NK cell product, reverses immune checkpoint inhibitor (ICB) resistance with synergistic anti-tumor activity (SITC 2023) - "Furthermore, WUNK synergized with ICB to enhance anti-tumor activity and rescue pembrolizumab resistance leading to a durable adaptive response. Overall, these findings provide a strong rationale for exploring the combination of WUNK with ICBs clinically to overcome immune evasion and improve patient outcomes."

Checkpoint inhibition • Oncology • Solid Tumor • Triple Negative Breast Cancer • IFNG

Wugen to Present New Clinical Data for WU-CART-007 and Preclinical Data for WU-NK-101, Two Investigational Allogeneic Cell Therapies for Challenging Hematologic Cancers, at American Society of Hematology Annual Meeting & Exposition (GlobeNewswire) - "Wugen, Inc...will be presenting four abstracts, now available online, at the American Society of Hematology (ASH) Annual Meeting and Exposition Dec. 9-12...In an oral presentation, Armin Ghobadi, M.D., from Washington University in St. Louis, will share data from study WU-CART-007 1001...In a second oral presentation, Sergio Rutella....will present pre-clinical findings for WU-NK-101, a cytokine-reprogrammed, expanded, cryopreserved, off-the-shelf, un-engineered memory-like NK cell product derived from peripheral blood mononuclear cells (PBMCs)."

P1/2 data • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

WU-NK-101, best in class memory-NK cell, has key features vital for adoptive cell therapy (ACT) in solid tumors (ST) (ESMO 2023) - "Conclusions We show that WUNK cells exhibit features that overcome challenges for ACT and enhances anti-tumor activity in ST, heralding the promise of NK cell therapy for ST. The data presented augurs positively for pts to be treated in the upcoming phase I/b clinical study."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NCAM1

Wugen Begins First-in-Human Phase 1 Clinical Trial of WU-NK-101, its Lead Allogeneic Memory Natural Killer (NK) Cell Therapy for Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (Businesswire) - "Wugen, Inc...announced that it has initiated patient dosing in the first-in-human Phase 1 clinical trial of WU-NK-101 for patients with relapsed or refractory (r/r) acute myelogenous leukemia (AML). Additionally, Wugen announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to WU-NK-101 for the treatment of AML."

Orphan drug • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

WUN101-01: A Phase 1 Study of WU-NK-101 in Patients With Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Wugen, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

A Phase 1b Study of WU-NK-101 in Combination With Cetuximab (clinicaltrials.gov) - P1b | N=30 | Not yet recruiting | Sponsor: Wugen, Inc. | Initiation date: May 2023 ➔ Nov 2023

Combination therapy • Metastases • Trial initiation date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • EGFR

A PHASE 1 STUDY OF WU-NK-101 IN PATIENTS WITH RELAPSED OR REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML) (EHA 2023) - P1 | "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"

Clinical • P1 data • Acute Myelogenous Leukemia • Atrial Fibrillation • Cardiovascular • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Renal Disease • IL2