KUR-501 / Baylor College of Medicine, Texas Children’s Hospital, Athenex - LARVOL DELTA

GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Baylor College of Medicine | Trial primary completion date: Jul 2025 ➔ Dec 2027

Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

IL-18 Metabolically Reprograms CAR-expressing Natural Killer T Cells and Enhancing Antitumor Activity Against Neuroblastoma (ASGCT 2025) - P1 | "After repeated in vitro tumor challenge, IL-18 or IL-15.IL-18 co-expressing GD2.CAR-NKT retained higher functionality (proliferation, cytotoxicity, and cytokine secretion) compared with IL-15 or no cytokine controls...These results provide support for using IL-18 for clinical development of the next generation of cytokine-armed CAR-NKT cancer immunotherapy. Disease Focus of Abstract:Cancer Solid Tumors"

Neuroblastoma • Oncology • Solid Tumor • IL12A • IL15 • IL18

PRDM1 is a key regulator of the natural killer T-cell central memory program and effector function. (PubMed, Cancer Immunol Res) - "In contrast, shRNA-mediated PRDM1 knockdown preserved effector function while promoting central memory differentiation, resulting in GD2.CAR NKTs with potent in vivo antitumor activity. Thus, we have identified PRDM1 as a regulator of NKT memory differentiation and effector function that can be exploited to improve the efficacy of NKT-based cancer immunotherapies."

Journal • CNS Tumor • Hematological Malignancies • Leukemia • Neuroblastoma • Oncology • Solid Tumor • GZMB • PRDM1

GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children with Neuroblastoma (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Baylor College of Medicine | N=36 ➔ 54

Enrollment change • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Baylor College of Medicine | Active, not recruiting ➔ Recruiting | Trial completion date: Aug 2034 ➔ Aug 2040 | Trial primary completion date: Jul 2023 ➔ Jul 2025

Enrollment open • Trial completion date • Trial primary completion date • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor

Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results. (PubMed, Nat Med) - P1 | "No dose-limiting toxicities occurred; one patient experienced grade 2 cytokine release syndrome that was resolved by tocilizumab. Additionally, their anti-tumor activity may be enhanced by targeting BTG1. ClinicalTrials.gov registration: NCT03294954 ."

Journal • P1 data • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • IL15

Immunai and Baylor College of Medicine Provide Updated Interim Phase 1 Results for anti-GD2 CAR NKT-Cell Therapy in Relapsed/Refractory Neuroblastoma (Businesswire) - P1 | N=36 | NCT03294954 | "BCM conducted extensive in vitro and in vivo studies to validate the superior anti-tumor activity of CAR-NKT cells modified to target BTG1, demonstrating the potential of this approach for use as a cutting-edge therapy. Importantly, CAR-NKT cells genetically modified to target BTG1 were able to overcome exhaustion, a major obstacle for developing effective cell therapy products."

P1 data • Neuroblastoma • Oncology • Solid Tumor

Harnessing CRISPR/Cas9 Mutagenesis Screening for Rational Design of Next-Generation CAR-NKT Therapy Against Neuroblastoma (ASGCT 2023) - P1 | "To address this gap, we have developed a CRISPR/Cas9 screening system to identify genes that regulate the persistence and antitumor activity of NKTs and GD2-CAR NKTs for therapeutic targeting... A CRISPR/Cas9-based screening system is feasible for use in human NKTs/CAR-NKTs to identify novel genes that regulate persistence and antitumor potential of NKTs in an unbiased manner. Results obtained from this study will ultimately help to enhance the antitumor efficacy of NKT cell-based cancer immunotherapy."

IO biomarker • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • SELL

Co-Expression of the IL15-IL15α Complex with a 41BB-Based Chimeric Antigen Receptor Promotes Superior Antitumor Activity in NKT Cells (ASGCT 2023) - "Therefore, we hypothesized that co-expressing IL15 and 15Rα (15.15Rα) in GD2.CAR NKTs will enhance their antitumor activity...Gene expression analysis after NB tumor cell challenge revealed that BBz.15.15Rα NKTs have a similar gene expression profile to naïve or central memory T cells while 28z.15.15Rα NKTs instead resemble exhausted T cells (p<0.05). Therefore, the BBz.15.15Rα construct has emerged as the leading candidate for the next-generation CAR-NKT cell therapy for NB."

CNS Tumor • Hematological Disorders • Hematological Malignancies • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • IL15

Athenex Provides Fourth Quarter and Full Year 2022 Financial Results and Business Update (GlobeNewswire) - "Recent FDA-imposed clinical hold of the KUR-501 Investigational New Drug Application (IND) following the death of a young heavily pretreated male patient with R/R HRNB treated at the fifth dose level of 300 million cells/m2 approximately three weeks after CAR-NKT cell therapy product administration....Anticipated Upcoming Milestones: Targeting Phase 1 GINAKIT2 study of KUR-501 reopening mid-2023, pending FDA potentially lifting clinical hold; Phase 1 GINAKIT2 dose escalation study safety and preliminary efficacy data update anticipated in 2H 2023....Next clinical trial data update from the ongoing ANCHOR and ANCHOR2 studies anticipated in 2H 2023....KUR-503: Allogeneic GPC3 CAR-NKT cell therapy for previously treated advanced GPC3-expressing hepatocellular carcinoma...IND application filing for the investigational treatment of adults with previously treated advanced GPC3-expressing hepatocellular carcinoma planned in 2024."

IND • P1 data • Trial suspension • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Liver Cancer • Lymphoma • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Baylor College of Medicine | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor

Athenex Provides Third Quarter 2022 Financial Results and Business Update (GlobeNewswire) - "Key Anticipated Milestones - (i) KUR-501: Phase 1 GINAKIT2 study dose escalation, safety, and preliminary efficacy data update in 1H 2023; (ii) KUR-502: Next clinical trial data update from the ongoing ANCHOR study anticipated in 1H 2023."

P1 data • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Solid Tumor

Anti-GD2 CAR NKT Cells Are Safe and Produce Antitumor Responses in Patients with Relapsed/Refractory Neuroblastoma (ASGCT 2022) - P1 | "CAR-NKTs are safe and can expand post-transfer, producing objective responses in NB patients. CAR-NKT antitumor activity is associated with in vivo rate of expansion and CD62L+ frequency in infused products. LEF1 maintains central memory-like differentiation in CD62L+ NKTs, and transgenic overexpression of LEF1 helps CAR-NKTs resist exhaustion and boosts therapeutic efficacy in a NB model."

Clinical • Neuroblastoma • Oncology • Solid Tumor • IL15 • LEF1 • SELL

GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Baylor College of Medicine | Trial primary completion date: Jul 2022 ➔ Jul 2023

Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

Athenex Provides Second Quarter 2022 Financial Results and Business Update (GlobeNewswire) - "Key Anticipated Milestones: Oral Paclitaxel: Phase 2 data from I-SPY 2 trial evaluating Oral Paclitaxel in combination with dostarlimab in neoadjuvant breast cancer expected in 2H 2022. Regulatory interactions with UK MHRA for Oral Paclitaxel in advanced breast cancer in UK remain on track with responses to questions expected later this quarter. KUR-501: autologous GD2 CAR-NKT cell therapy for relapsed/refractory high-risk neuroblastoma...Next data update from the ongoing GINAKIT2 study expected in 2023. KUR-502: allogeneic CD19 CAR-NKT cell therapy for relapsed/refractory B-cell malignancies. Ongoing multicenter expansion of Phase 1 dose escalation ANCHOR study. Next clinical trial data update from the ongoing ANCHOR study anticipated in 4Q 2022 or 1Q 2023. KUR-503: IND filing for KUR-503 in GPC3-expressing hepatocellular carcinoma planned in 2023."

European regulatory • IND • P1 data • P2 data • Breast Cancer • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Neuroblastoma • Oncology

Athenex, Texas Children’s Cancer Center, and the Center for Cell and Gene Therapy at Baylor College of Medicine to Present Phase 1 Clinical Data for KUR-501, an autologous GD2 CAR-NKT Cell Therapy for Relapsed/Refractory High Risk Neuroblastoma at the ASGCT 25th Annual Meeting (GlobeNewswire) - P1 | N=36 | GINAKIT2 (NCT03294954) | "Data demonstrate expansion of CAR-NKT cells post-transfer in all patients, and objective responses in patients with relapsed/refractory neuroblastoma. Evidence of therapeutic efficacy with 25% (3/12) Overall Response Rate (ORR), 58% (4 stable disease, 2 partial responses, 1 complete response/12) Disease Control Rate (DCR), and 2 out of 3 responses at dose level 4 (1x108/m2). Durable Complete Response persisting 12 months. Analysis found that responders correlate with CD62L+ NKT frequency in the pre-infusion products as well as CAR-NKT area under the curve (AUC) in the peripheral blood post-infusion."

P1 data • Neuroblastoma • Oncology • Solid Tumor

GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Baylor College of Medicine | N=24 ➔ 36

Enrollment change • Neuroblastoma • Oncology • Solid Tumor

Athenex Provides Fourth Quarter and Full Year 2021 Financial Results and Provides Business Update (GlobeNewswire) - "Key Anticipated Milestones: Update on ANCHOR data previously presented at ASH in 2021 at ASTCT on April 23-26, 2022; Update from KUR-501, our autologous program in pediatric neuroblastoma at the American Society of Gene & Cell Therapy (ASGCT) annual meeting on May 16-19, 2022; Expand CD19 CAR-NKT ANCHOR study to a multi-center study under the newly allowed IND; Potential regulatory update from MHRA for Oral Paclitaxel in metastatic breast cancer (mBC) in UK."

Clinical • Clinical data • European regulatory • P1 data • Trial status • Breast Cancer • Neuroblastoma • Oncology

GINAKIT2: GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Baylor College of Medicine; Trial primary completion date: Sep 2021 ➔ Jul 2022

Clinical • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

Athenex and the Center for Cell and Gene Therapy Announce Allowance of Our First U.S. Patent Claims Around CAR-NKT Cell Therapy (GlobeNewswire) - "Athenex...the leading developer of NKT cell therapy and the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital today announced that the U.S. Patent and Trademark Office has allowed patent claims around its NKT cellular immunotherapy platform. While similar claims had already been granted in the European Union, these claims are the first allowed on this technology in the U.S."

Patent • Oncology

Athenex, Texas Children’s Cancer Center, and the Center for Cell and Gene Therapy at Baylor College of Medicine Present New Clinical Data on GD2 CAR-NKT Cells in Neuroblastoma at ASGCT Annual Meeting (GlobeNewswire) - P1, N=24; GINAKIT2 (NCT03294954); “Athenex, Inc…announced that investigators from Texas Children’s Cancer Center and the Center for Cell and Gene Therapy at Baylor College of Medicine presented new clinical data from the ongoing GINAKIT2 phase 1 study of Athenex’s cell therapy candidate KUR-501 targeting GD2 in neuroblastoma at the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting on Friday, May 14, at 11 am ET. Observed responses to date in 11 evaluable, heavily pretreated patients with neuroblastoma, include one complete response (CR) and one partial response (PR). Four additional patients have exhibited stable disease (SD). The durations of response for the CR and PR were approximately 5 and 3 months, respectively. No patients experienced grade 2 or higher toxicities related to the GD2-CAR NKTs. Post-treatment tumor biopsies showed GD2-CAR NKTs homing to metastatic lesions at all dose levels.”

P1 data • Neuroblastoma • Oncology

Kuur Therapeutics Announces Interim Clinical Data Supporting CAR-NKT Cell Therapy Platform (Businesswire) - P1, N=24; GINAKIT2 (NCT03294954); "In the GINAKIT2 study, out of ten evaluable patients and with escalation to a dose level (DL) of 1x108 cells/m2, one complete response (CR) and one partial response (PR) have been observed to date, with stable disease (SD) in three additional patients....KUR-501 has so far demonstrated a promising safety profile, with only one case of grade two cytokine release syndrome (CRS) and no cases of immune effector cell-associated neurotoxicity syndrome (ICANS)."

Cytokine release syndrome • P1 data • Neuroblastoma • Oncology

Kuur Therapeutics Announces Publication of Interim Phase 1 Data for CAR-NKT Cell Therapy KUR-501 in Nature Medicine (Businesswire) - P1, N=24; GINAKIT2 (NCT03294954); Sponsor: Baylor College of Medicine; "The interim results demonstrated that expressing the CAR with interlukin-15 (IL-15), a natural protein that supports NKT survival, enhanced the tumor-fighting capabilities and in vivo persistence of autologous NKT cells. Two of three patients studied showed tumor reduction following CAR-NKT infusion: one classified as stable disease and the other as a partial response. Imaging revealed a dramatic reduction in the size and metabolic activity of bone metastases in the patient with the partial response."

P1 data • Neuroblastoma • Oncology

Cell Medica Collaborators, Baylor College of Medicine and Texas Children’s Hospital, present positive early patient data from CAR-NKT neuroblastoma trial at American Society Of Gene & Cell Therapy 22nd Annual Meeting (Businesswire) - P1, N=24; GINAKIT2 (NCT03294954); "Early data from the first two patients at the lowest dose level (3 x 106 CAR-NKT cells/m2) showed substantial in vivo expansion of CAR-NKT cells and subsequent infiltration of CAR-NKT cells into both the solid tumor mass and bone marrow....GINAKIT2 Phase 1 trial is evaluating GD2 targeted CAR-NKT therapy, CMD-501, in children with relapsed or refractory (R/R) high risk neuroblastoma"

P1 data

Newly added product (Businesswire) - P1, Oncology

Pipeline update