NIB102 / Noile-Immune Biotech - LARVOL DELTA

TAK-102-1501: A Study of TAK-102 in Adult With Previously-Treated Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: Takeda | Trial completion date: Jul 2026 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2026 ➔ May 2025; Business decision unrelated to patient safety

Trial completion date • Trial primary completion date • Trial termination • Solid Tumor • GPC3

Quantitative clinical pharmacology and mechanistic modeling of TAK-102, a GPC3 targeted CAR-T therapy armored with IL-7 and CCL19, in a phase-1 clinical trial in solid tumor patients (SITC 2024) - P1 | "Methods As of March 31st, 2024, 11 patients have been infused with TAK-102 at dose-levels of 10 million (DL1), 100 million (DL2) and 500 million (DL3) CAR+ cells/patient after standard lymphodepletion chemotherapy regimen of cyclophosphamide and fludarabine...Results Among the 11 patients treated so far, no DLT or neurotoxicity was observed, whereas 6/11 patients experienced mild cytokine release syndrome (CRS, mostly grade 1) managed by appropriate medications (e.g., tocilizumab), suggesting acceptable safety profile of TAK-102...A mechanistic PBCK-PD model was able to adequately integrate dataset(s) pertaining to extent of lymphodepletion, homeostatic cytokines, TAK-102 CK, tumor volume and key biomarker measurements by goodness of fits. Conclusions The integrated CK-PD analysis presented here could facilitate identification of relative contribution of factors impacting exposure/response of TAK-102 and help understand the mechanism of action of this therapy to..."

Clinical • IO biomarker • P1 data • Hepatocellular Cancer • Oncology • Solid Tumor • AFP • CCL19 • GPC3 • IFNG • IL6 • IL7

Quantitative clinical pharmacology and mechanistic modeling of TAK-102, a GPC3 targeted CAR-T therapy armored with IL-7 and CCL19, in a phase-1 clinical trial in solid tumor patients (SITC 2024) - P1 | "Methods As of March 31st, 2024, 11 patients have been infused with TAK-102 at dose-levels of 10 million (DL1), 100 million (DL2) and 500 million (DL3) CAR+ cells/patient after standard lymphodepletion chemotherapy regimen of cyclophosphamide and fludarabine...Results Among the 11 patients treated so far, no DLT or neurotoxicity was observed, whereas 6/11 patients experienced mild cytokine release syndrome (CRS, mostly grade 1) managed by appropriate medications (e.g., tocilizumab), suggesting acceptable safety profile of TAK-102...A mechanistic PBCK-PD model was able to adequately integrate dataset(s) pertaining to extent of lymphodepletion, homeostatic cytokines, TAK-102 CK, tumor volume and key biomarker measurements by goodness of fits. Conclusions The integrated CK-PD analysis presented here could facilitate identification of relative contribution of factors impacting exposure/response of TAK-102 and help understand the mechanism of action of this therapy to..."

Clinical • IO biomarker • P1 data • Hepatocellular Cancer • Oncology • Solid Tumor • AFP • CCL19 • GPC3 • IFNG • IL6 • IL7

CAR-T therapy (NIB102) powered by NoilImmune's PRIME technology Quantitative clinical pharmacology analysis and mechanistic model in phase I clinical trials Poster presentation at the American Society for Immunotherapy of Cancer (SITC) [Google translation] (Noile-Immune Biotech Press Release) - P1 | N=11 | NCT04405778 | Sponsor: Takeda | "Regarding an update on the results of the Phase I dose-escalation first-inhuman trial...In 11 patients treated with NIB102 (TAK-102), DLT (dose-limiting toxicity), neurotoxicity neither gender was recognized. All recognized cytokine release syndromes (CRS) are NIB102 is grade 1 and manageable up to dose 3 (5 × 10⁸ CAR-T cells/person)...Best response achieved SD (stable disease) in 5 patients as assessed by the investigator...Exposure from dose 1 (1×10⁷ CAR-T cells/person) to dose 2 (1×10⁸ CAR-T cells/person) (Cmax/AUC) and a decrease in Tmax values ​​from dose 2 (1×10⁸ CAR-T cells/person) to dose 3 (5×10⁸ CART cells/person)....interim data (n=11) indicate that the immunogenicity of NIB102 (TAK-102) affects cell dynamics and efficacy. No signs of deterioration were observed."

Cytokine release syndrome • P1 data • Oncology • Solid Tumor

A Study of TAK-102 in Adult With Previously-Treated Solid Tumors (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Dec 2026 ➔ Jul 2026 | Trial primary completion date: Dec 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • GPC3

Regarding the return of NIB102 and NIB103 from Takeda Pharmaceutical [Google translation] (Noile-Immune Biotech Press Release) - "As announced on December 15, 2023, the Company has expanded its in-house drug discovery pipeline, NIB102 and Regarding NIB103 and NIB103, Takeda Pharmaceutical...which was the out-licensing partner, has provided support regarding the development and commercialization of NIB103 and NIB103. However, on June 22, discussions with the company regarding data transfer, etc., were completed...Due to the return of both pipelines, the Phase I study conducted by Takeda Pharmaceutical will be subject to future new patients. Patients will not be enrolled and will remain under Takeda's supervision until post-administration follow-up is completed and the clinical trial is completed. Therefore, there will be no financial burden on our company regarding the completion of this Phase I study....In addition, regarding NIB103, Takeda Pharmaceutical will We will pay Takeda a low-single-digit royalty after market launch for the use of Takeda's proprietary intellectual property."

Licensing / partnership • Oncology • Solid Tumor

Updated results from first-in-human phase 1 dose-escalation trial of TAK-102, a GPC3-targeted armored CAR T cells, in patients with advanced solid tumors. (ASCO 2024) - P1 | "TAK-102 was administered via a single infusion to 3 dose cohorts after lymphodepleting chemotherapy (LDC; consisting of fludarabine and cyclophosphamide): dose level (DL) 1 (starting cohort), 1x10 7 CAR+ cells/body; DL2, 1x10 8 CAR+ cells/body; DL3, 5x10 8 CAR+ cells/body. TAK-102, an armored CAR-T, is well tolerated and has a manageable safety profile with some early signs of anti-tumor activity. For CK, TAK-102 exposure (Cmax, AUC) showed improvement from DL1 to DL2, and slight decrease in Tmax from DL2 to DL3. Dose-dependency was observed in peak CCL19, IFN-γ and IL-6 levels, which may point towards increased signal of activity from DL1 to DL3."

CAR T-Cell Therapy • Clinical • IO biomarker • Metastases • P1 data • Endocrine Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Neuroendocrine Tumor • Oncology • Sarcoma • Solid Tumor • CCL19 • GPC3 • IFNG • IL6 • IL7

Noile-Immune - Continued strong growth, reports results of clinical trial of autologous CAR-T cell therapy for solid tumors at US academic conference [Google translation] (Yahoo Finance) - P1 | N=11 | NCT04405778 | Sponsor: Takeda | "Noile -Immune...company announced that the results of a Phase 1 clinical trial targeting solid tumors for its autologous CAR-T cell therapy (NIB102) incorporating its own technology were reported at the American Society of Clinical Oncology Annual Meeting. No dose-limiting toxicity was observed, and results suggested efficacy, such as antitumor effects and tumor shrinkage in patients with hepatocellular carcinoma. Going forward, development and commercialization rights will be returned to the company by Takeda Pharmaceutical Co., Ltd...and development will be led by Noile-Immune Biotech."

Licensing / partnership • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Takeda drops cancer candidates, axing immunocytokine and CAR-Ts amid shifting treatment landscape (Fierce Pharma) - "Takeda’s vision of becoming a leader in oncology ran into more trouble Thursday when the drugmaker axed (PDF) a midphase immunocytokine and three early-stage CAR-T cell therapy prospects from its R&D pipeline...Takeda pushed modakafusp alfa out of the door as part of a pipeline clear-out that also hit three phase 1 autologous CAR-T candidates. Two of the prospects, GPC3-targeted TAK-102 and mesothelin-directed TAK-103, were in development in solid tumors. The third asset, TAK-940, was a CD19-directed, Memorial Sloan Kettering Cancer Center-partnered program that used the 1XX domain to try to enhance efficacy....While Takeda axed a clutch of cancer candidates, Plump said the company 'remains committed to oncology and will continue to develop therapies across hematologic and solid tumors.'"

Discontinued • Hematological Malignancies • Oncology • Solid Tumor

A Study of TAK-102 in Adult With Previously-Treated Solid Tumors (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting | N=18 ➔ 11

Enrollment change • Enrollment closed • Oncology • Solid Tumor • GPC3

Announcement on the Termination of License Agreement for NIB102 and NIB103 (Noile-Immune Biotech Press Release) - "Noile-Immune Biotech, Inc...hereby announces that Noile-Immune received the following notification today regarding the license agreements with Takeda: Takeda has decided to terminate the license agreement for NIB102 (TAK102) and NIB103 (TAK103), thereby returning the rights for the development and commercialization of NIB102 and NIB103 to Noile-Immune; The reason for the termination of the license agreement for NIB102 and NIB103 is due to a strategic shift in Takeda’s development portfolio towards allogeneic cell therapies, and is not related to any concerns about the safety or efficacy of NIB102 and NIB103....As a consequence of this termination, Noile-Immune will hold the rights of NIB102 and NIB103. Noile-Immune is going to discuss with Takeda regarding the transition of ongoing trials, transfer of the obtained data, handling of intellectual property rights, and settlement of termination fee paid by Takeda, so as to explore future options."

Licensing / partnership • Oncology • Solid Tumor

Development and application of physiologically based pharmacokinetic – pharmacodynamic (PBPK-PD) model for dose optimization of TAK-102: GPC3 targeted CAR-T armored with IL-7 and CCL-19 (SITC 2023) - "Results The K-PD model was able to describe the host T-lymphocytes recovery kinetics post lymphodepleting chemotherapy (Fludarabine with Cyclophosphamide). Conclusions The developed model was able to describe the observed data, while accounting for tumor heterogeneity of CAR-T cells, impact of lymphodepletion regimen on CAR-T expansion and target-mediated expansion of effector CAR-T cells. Using model simulations, CAR-T expansion was found to be driven by initial tumor burden and GPC3 expression."

IO biomarker • PK/PD data • Oncology • Solid Tumor • GPC3 • IL7

Interim results of FIH Phase 1 of TAK-102, GPC-3 targeted armored CAR-T therapy in patients with advanced solid tumors (JSMO 2023) - No abstract available

Clinical • Metastases • P1 data • Oncology • Solid Tumor • GPC3

A Study of TAK-102 in Adult With Previously-Treated Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Takeda | Trial completion date: Jul 2023 ➔ Dec 2026 | Trial primary completion date: Jul 2023 ➔ Dec 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • GPC3

Interim results of a first-in-human Phase 1 dose-escalation trial of TAK-102, a glypican-3 targeted armored chimeric antigen receptor T-cell immunotherapy in patients with advanced solid tumors (SITC 2022) - P1 | "TAK-102 is administered via a single infusion on 3 dose cohorts after lymphodepleting chemotherapy (fludarabine and cyclophosphamide): Cohort 1 (starting cohort), 1x10 7 CAR+ cells/body; Cohort 2, 1x10 8 CAR+ cells/body; Cohort 3, 1x10 9 CAR+ cells/body. Preliminary data show an encouraging safety profile and CK/PD results. The dose-escalation study is ongoing ( NCT04405778 )."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Cervical Cancer • Endocrine Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liposarcoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • AFP • CCL19 • CD69 • GPC3 • GPI • GZMB • IFNG • IL10 • IL12A • IL7

A Study of TAK-102 in Adult With Previously-Treated Solid Tumors (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Takeda; Trial completion date: Nov 2022 ➔ Jul 2023; Trial primary completion date: Nov 2022 ➔ Jul 2023

Clinical • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • GPC3

Takeda Opens New R&D Cell Therapy Manufacturing Facility to Support Expansion of Next-Generation Clinical Programs (Takeda Press Release) - "Takeda Pharmaceutical Company Limited...announced the expansion of its cell therapy manufacturing capabilities with the opening of a new 24,000 square-foot R&D cell therapy manufacturing facility at its R&D headquarters in Boston...Takeda and MD Anderson are developing a potential best-in-class allogeneic cell therapy product (TAK-007), a Phase 1/2 CD19-targeted chimeric antigen receptor-directed natural killer (CAR-NK) cell therapy with potential for off-the-shelf use being studied in patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Two additional Phase 1 studies of Takeda cell therapy programs were also recently initiated: 19(T2)28z1xx CAR T cells (TAK-940)...to treat relapsed/refractory B-cell cancers, and a cytokine and chemokine armored CAR-T (TAK-102)....to treat GPC3-expressing previously treated solid tumors."

Clinical • Trial status • Chronic Lymphocytic Leukemia • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Study of TAK-102 in Adult Patients With GPC3-Expressing Previously Treated Solid Tumors (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Takeda; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Oncology • Solid Tumor

A Study of TAK-102 in Adult Patients With GPC3-Expressing Previously Treated Solid Tumors (clinicaltrials.gov) - P1; N=18; Not yet recruiting; Sponsor: Takeda

Clinical • New P1 trial • Oncology • Solid Tumor