Hyleukin-7 (efineptakin alfa) / Genexine, NeoImmuneTech, I-Mab, PT Kalbe Farma - LARVOL DELTA

NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | N=12 ➔ 18

Enrollment change • CNS Disorders • Rare Diseases • CD4

GX-I7, a long-acting IL-7, safely and effectively increased peripheral CD8+/CD4+ T cells and TILs in patients with locally advanced or metastatic solid tumours. (PubMed, Br J Cancer) - P1b | "Findings suggest GX-I7 is a safe T cell-amplifying agent with peripheral immune activation. Ongoing studies are exploring its ability to enhance immune responses in peripheral immune cells and tumour cells when combined with other anti-cancer agents."

Journal • Oncology • Solid Tumor • CD4 • CD8 • IL7

Dose Optimization of rhIL-7-hyFc for Patients With Lymphopenia Using a Neonatal Fc Receptor-Mediated Recycling-Based and Target-Mediated Drug Disposition Pharmacokinetic Model. (PubMed, Clin Transl Sci) - "Based on the simulation results, 670-800 μg/kg every 3 weeks, 1010-1530 μg/kg every 6 weeks, and 1510-2190 μg/kg every 9 weeks IM were proposed. These results may help further understand rhIL-7-hyFc characteristics and, moreover, provide guidance for selecting the appropriate dosing regimen in future clinical trials."

Clinical • Journal • PK/PD data • Oncology

NeoImmuneTech's high-dose CAR-T combo for lymphoma hits 100% ORR (Korea Biomedical Review) - P1 | N=57 | NCT05075603 | Sponsor: NeoImmuneTech | "Headquartered in Maryland, the U.S., with a Korean subsidiary in Bundang, the biotech on Monday released topline results from NIT-112, a U.S. trial evaluating NT-I7 (efineptakin alfa) in 17 patients with relapsed or refractory large B-cell lymphoma....Regulatory documents released the same day showed that among the seven dose levels tested, the clearest signal came in the 480 to 720 μg/kg group. All eight patients in that cohort achieved a 100 percent overall response rate (ORR), including six complete responses (CR) and two partial responses. Six had complete responses and two had partial responses, including one patient who later converted to a CR. By the six-month mark, seven of the eight remained in response."

P1 data • Diffuse Large B Cell Lymphoma

ORAL ABSTRACT Treatment of Autosomal Recessive Interleukin-7 Deficiency with NT-I7 (Efineptakin Alfa), Long-Acting Recombinant Human Interleukin-7: An Expanded Access Protocol (CIS 2025) - "The ex vivo anti-apoptotic and proliferative effect of IL-7 on T cells from patients with IL-7 deficiency raises the promising possibility that NT-I7 will have a similar effect in vivo in this as well as other inborn errors of immunity associated with impaired T cell homeostasis. Figure 1. Baseline CD127 expression, phosphorylated STAT5 and BCL2 signal transduction with IL-7 stimulation, and T cell proliferation assays in IL-7– deficient patients as compared with healthy controls."

Clinical • IO biomarker • Genetic Disorders • Immunology • Infectious Disease • Non-melanoma Skin Cancer • Oncology • Primary Immunodeficiency • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • BCL2 • CD31 • CD4 • CD8 • IL7 • IL7R • PECAM1 • STAT5

NeoImmuneTech Demonstrates Lymphocyte Recovery and Antitumor Enhancement of NT-I7 at AACR 2025 [Google translation] (BioTimes) - "NeoImmuneTech...announced on the 25th that it plans to present research results proving that NT-I7 (Efineptakin alfa) restores lymphocyte counts and enhances anticancer effects in a non-clinical model of head and neck squamous cell carcinoma (HNSCC) at the American Association for Cancer Research (AACR 2025), to be held in Chicago, USA from the 25th to the 30th....NT-I7 significantly restored the reduced numbers of CD4+, CD8+ T cells and NKT cells in the HNSCC tumor mouse model, while having no significant effect on Tregs (regulatory T cells) in tumor tissues. In the MOC22 tumor model, it showed high tumor growth inhibition efficacy even when administered alone, and in the MOC1 tumor model, NT-I7 and cisplatin combination showed significant antitumor efficacy."

Preclinical • Squamous Cell Carcinoma of Head and Neck

NT-I7 increases lymphocytes and enhances chemotherapy and immunotherapy efficacy in HNSCC (AACR 2025) - "NT-I7 effectively increases lymphocyte populations in HNSCC preclinical models that demonstrate tumor-associated lymphopenia, and enhances the efficacy of cisplatin and anti-PD-1 in HNSCC preclinical tumor models."

Clinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • IL7

rhIL-7-hyFc on Increasing Lymphocyte Counts in Patients With Newly Diagnosed Non-severe Lymphopenic Gliomas Following Radiation and Temzolomide (clinicaltrials.gov) - P1/2 | N=42 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial primary completion date: Feb 2025 ➔ May 2025

Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1 • MGMT

Correction: rhIL-7-hyFc, a long-acting interleukin-7, improves efficacy of CAR-T cell therapy in solid tumors. (PubMed, J Immunother Cancer) - No abstract available

Journal • Oncology • Solid Tumor • IL7

NeoImmuneTech leads Korea’s biotech bloodbath as IPO firms shed billions on failed promises (Korea Biomedical Review) - "The company is pushing forward with preclinical trials in non-human primates through Charles River Laboratories and met with the FDA in February 2025 to confirm its study design. 'If we proceed as planned, we expect interim results by mid-2025 and aim to complete the necessary experimental data by year-end,'..."

Preclinical • Oncology

NT-I7 for the Treatment of Recurrent Squamous Cell Carcinoma of Head and Neck Undergoing Surgery (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Hyunseok Kang, MD | N=10 ➔ 4 | Recruiting ➔ Terminated; Slow Accrual

Enrollment change • IO biomarker • Trial termination • Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma. (PubMed, J Immunother Cancer) - P1 | "Preliminary data demonstrate safety and activity of IL-7 in patients with KS and activity specifically among individuals HIV-associated KS."

Journal • P1 data • Genetic Disorders • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Kaposi Sarcoma • Oncology • Sarcoma • Skin Cancer • Solid Tumor • CD4 • CD8

NeoImmuneTech, JP Morgan Healthcare Participation “Discuss NT-I7 and CAR-T Combination Technology Transfer” [Google translation] (Hankyung) - "NeoImmuneTech announced on the 7th that it will participate in the 'JP Morgan Healthcare Conference' held in San Francisco, USA from January 13th to 16th. At this event, the company plans to begin full-scale technology transfer discussions with global pharmaceutical companies based on the results of the T cell booster NT-I7 (Efineptakin alfa) and CAR-T treatment combination clinical trial (NIT-112)."

Commercial • Large B Cell Lymphoma

rhIL-7-hyFc on Increasing Lymphocyte Counts in Patients With Newly Diagnosed Non-severe Lymphopenic Gliomas Following Radiation and Temzolomide (clinicaltrials.gov) - P1/2 | N=42 | Active, not recruiting | Sponsor: Washington University School of Medicine | Recruiting ➔ Active, not recruiting | N=70 ➔ 42 | Trial primary completion date: Jan 2032 ➔ Feb 2025

Enrollment change • Enrollment closed • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1 • MGMT

NT-I7, a Long-Acting Interleukin-7 Molecule, Promotes T Cell Reconstitution Following Radiation Injury through Thymic-Dependent and Independent Pathways (ASH 2024) - "The result demonstrated that treatment with NT-I7 also significantly shortened the time required for rejection of the 2nd skin graft compared with the vehicle control group, demonstrating that NT-I7 can also promote functional memory T cell responses in vivo. These results indicate that NT-I7 is a promising therapeutic for significantly accelerating recovery of functional T cells after radiation exposure."

Hematological Disorders • Infectious Disease • CD24 • CD8 • GZMB • IFNG • IL7 • TNFA

Efineptakin Alfa and Pembrolizumab for the Treatment of Recurrent Glioblastoma (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Mayo Clinic | Trial completion date: Oct 2025 ➔ Oct 2028 | Trial primary completion date: Oct 2024 ➔ Oct 2027

Trial completion date • Trial primary completion date • Tumor mutational burden • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

A biomarker signature differentiates immune status in patients with cold gastrointestinal tumors, predicting clinical benefit of NT-I7 (efineptakin alfa, a long-acting interleukin-7) and pembrolizumab (SITC 2024) - P1/2 | "Ethics Approval This trial obtained approval from MD Anderson IRB (2020-0008), Advarra IRB (IRB00000971), and Mary Crowley IRB (20–13). Participants gave informed consent before participating in this trial."

Biomarker • Clinical • IO biomarker • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • CXCL8 • IL7 • IL7R • PD-1

A first-in-human (FIH) phase I clinical trial assessing a therapeutic DNA vaccine, BG-210, in combination with long-acting IL-7 (GX-I7) and pembrolizumab for immunotherapy of mCRPC (SITC 2024) - "Conclusions These data suggest that BG-210 in combination with GX-I7 dual therapy or with pembrolizumab triple therapy has an acceptable safety profile. Additionally, BG-210 induces meaningful immune and PSA responses in mCRPC patients."

Clinical • Combination therapy • Late-breaking abstract • P1 data • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • IFNG • IL7

NeoImmuneTech Secures Final Safety of NT-I7 and CAR-T Treatment Combination Clinical Trial [Google translation] (NeoImmuneTech Press Release) - "NeoImmuneTech...announced that it has verified the safety of NT-I7 (efineptakin alfa) and CAR-T treatment combination phase 1b clinical trial (NIT-112)...The Data and Safety Monitoring Board (DSMB) analyzed the data of 17 patients who completed the combination therapy with CAR-T therapy and NT-I7 in the NIT-112 clinical trial and confirmed that the maximum dose of NT-I7, 720 ug/kg, can be used safely and recommended that this be set as the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)...In this clinical trial, the only serious adverse reaction (SAR) considered to be related to NT-I7 was fever, which was grade 1 (the lowest severity grade)...The DSMB concluded that the existing safety and tolerability of NT-I7 were confirmed at the highest dose of 720 ug/kg in the phase 1b clinical trial, and that the safety profile was maintained in combination with CAR-T....NeoImmuneTech plans to complete the phase 1b clinical trial of its CAR-T combination therapy..."

DSMB • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CYTOKINE-BASED IMMUNOTHERAPY WITH LONG-ACTING HUMAN RECOMBINANT IL-7 IN HPV-RELATED DISEASES (IPVC 2024) - "IL-7 genetic deficiency and ICL have distinct clinical and immunological features including difference in the proportion of Mucosal-Associated Invariant T-cells in peripheral blood and distribution of skin-resident memory T cells. NT-I7 treatment resulted in consistent and prolonged T-cell reconstitution in ICL. A role of IL-7 as neo-adjuvant immunological therapy for skin and mucosal HPV-related diseases in immunocompromised hosts deserves further clinical evaluation."

IO biomarker • Infectious Disease • Oncology • CD4 • CD8 • IL7

NT-I7, a long-acting interleukin-7, promotes activation, cytotoxic function, and selective clonotype expansion of CD8+ T cells in patients with high grade gliomas (SNO 2024) - P1/2 | "A subset of 4 subjects with glioblastoma multiforme (GBM) treated at 720 µg/kg of NT-I7 during adjuvant temozolomide in our study (NCT03687957) underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) of peripheral blood. NT-I7 promotes activation, cytotoxic function, and selective clonotype expansion of CD8+ T cells in patients with HGG. This, combined with its role in increased CD4+ T cell counts, suggests NT-I7 may be a powerful tool to restore immune function after treatment-associated lymphopenia in HGG."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oncology • Solid Tumor • CD4 • CD74 • CD8 • GZMA • GZMB • HLA-DRA • HLA-DRB1 • IL7 • JUNB • PRF1

Phase II trial of rhIL-7-hyFc in patients with high-grade glioma demonstrated acceptable safety profile and reduced lymphopenia (SNO 2024) - "rhIL-7-hyFc is safe and effective in improving ALC and CD4 count in patients with newly diagnosed HGG undergoing temozolomide and concurrent radiation therapy. This study was powered to meet the primary endpoint; larger trials will likely be required to demonstrate clinical efficacy. Nevertheless, these data support the continued exploration of rhIL-7-hyFc as an adjunct to standard therapy to mitigate lymphopenia and potentially extend survival for patients with HGG."

Clinical • Lymphopenia • P2 data • Brain Cancer • CNS Tumor • Fatigue • Glioblastoma • Glioma • Hematological Malignancies • Infectious Disease • Malignant Glioma • Oncology • Solid Tumor • CD4 • IL7 • MGMT

IL-7 stimulation remodels the tumor immune microenvironment in lung adenocarcinoma (SITC 2024) - "The mice received weekly treatments of either NT-I7 (efineptakin alfa, a recombinant human IL-7 agonist) or a vehicle control for 2 weeks...Through this spatial and molecular biology study, potential mechanisms underlying the enhancement of lymphocyte infiltration by IL-7 agonist therapy in lung cancer are unveiled, crucial for improving clinical efficacy of immunotherapy. Moreover, the upregulation of Cd274 in IL-7-treated mice suggests a potential synergy between IL-7 and PD-1/PD-L1 checkpoint blockade therapy."

IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCR7 • CD3E • CD63 • CXCL10 • IL7 • ITGAL • LAMP3 • TNFRSF4

NeoImmuneTech Announces Latest NT-I7 Research Results at SITC in the US [Google translation] (NeoImmuneTech Press Release) - "NeoImmuneTech is set to announce the results of a biomarker analysis of its NIT-110 clinical trial combining NT-I7 ( chemical name: efineptakin alfa) and Keytruda (PD-1 inhibitor). This biomarker analysis of NIT-110 is an additional research analysis based on data presented at ASCO 2024, and the company stated that it is continuing the search for biomarkers that can identify patient groups who are likely to benefit from the clinical efficacy of the NT-I7 and Keytruda combination treatment."

Biomarker • P1/2 data • Oncology • Solid Tumor

NeoImmuneTech to Present Research Results at 'Cytokines 2024 & KAI 2024' [Google translation] (NeoImmuneTech Press Release) - "According to the study, when NT-I7 was administered, the number of tumor-infiltrating lymphocytes increased, and in particular, bystander T cells also increased and became activated. It was confirmed that the anticancer effect of T cell engager was maximized as the tumor environment changed by NT-I7 improved...After NT-I7 treatment, it was confirmed that stem cell-like CD8 T cells...which mainly exist in lymphoid organs, increased in circulating blood and peripheral tissues. Tpex is a precursor of CD8 T cells that is important for immune checkpoint inhibitor treatment and plays a key role in antiviral and anticancer treatment, and NT-I7 promoted the proliferation of this Tpex, maximizing the effect of anti-PD-L1 and IL-2 combination therapy...Professor Seung....announced the results of a study that enhanced the efficacy of immune checkpoint inhibitors by restoring the number of T cells through the administration of NT-I7 in a lymphopenic environment."

Preclinical • Oncology • Solid Tumor