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

IL7-TBRII, a Dual Cytokine Modulator Targeting IL-7 and TGF-β Pathways, Inhibits Tumor Progression and Metastasis. (PubMed, Immune Netw) - "As TGF-β impairs CD8+ T cell function and antagonizes IL-7 signaling, we developed a bifunctional fusion protein, recombinant human IL-7 (rhIL-7)-hyFc-sTBRII (IL7-TBRII), by fusing a TGF-β trap (Fc-TBRII) to rhIL-7-hyFc (IL7-Fc)...Furthermore, IL7-TBRII reduced metastasis in the 4T1 breast cancer model by reshaping the immune cell composition, and demonstrated synergistic efficacy when combined with radiotherapy or anti-CTLA-4 therapy in the EMT6 breast tumor model. These findings suggest that dual modulation of the IL-7 and TGF-β pathways by IL7-TBRII effectively reprograms the immune microenvironment in both primary and metastatic tumors, particularly by promoting CD8+ T cell activation and infiltration, thus offering a promising strategy to improve clinical responses to immunotherapy."

Journal • Breast Cancer • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD8 • IL7 • TGFB1 • TGFBR2

NeoImmuneTech Presents Phase 1 Results of NT-I7 Combination Therapy at the American Society of Hematology [Google translation] (HIT News) - "As a result supporting this, the NT-I7 high-dose patient group (480 μg/kg or more, n=8) showed an objective response rate (ORR) of 100%, and 88% of patients showed a sustained response at 6 months. Additionally, the Kaplan-Meier-based overall survival (OS) analysis showed long-term survival results of 100% at 6 months, 62.9% at 12 months, and 53.9% at 24 months."

P1 data • Diffuse Large B Cell Lymphoma

Dex and IL-7 enhance persistence of CAR T cells to promote long-term remission in mouse models of multiple myeloma (ASH 2025) - "We previously found that dexamethasone (dex)administered ex vivo during manufacturing or in vivo during therapy upregulates IL7R alpha expressionon CAR T cells, can increase persistence and overall efficacy of CAR T cells when combined withexogenous IL-7 and importantly, does not inhibit CAR T cell expansion or activity. Combining CAR T cells with dex and NT-I7 significantly enhanced antitumor efficacy of CAR Tcell therapy for primary and extramedullary, leading to deep remission in both models."

CAR T-Cell Therapy • IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • IL7 • IL7R

A Phase 1 study evaluating NT-I7 (efineptakin alfa), a long-acting human IL-7, post-tisagenlecleucel (tisa-cel), post-axicabtagene ciloleucel (axi-cel), or post-lisocabtagene maraleucel (liso-cel) in Relapsed/Refractory large B-cell lymphoma (ASH 2025) - P1 | "NT-I7 at 720 μg/kg was determined to be the RP2D.Correlative data suggest earlier NT-I7 administration post-CART19 infusion may better optimize CART19expansion. Further studies investigating an earlier administration schema are needed."

P1 data • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • CD4 • CD8 • IL1B • IL5 • IL6 • IL7

NT-I7 (Efineptakin Alfa), a Long-acting Human IL-7, Post-Yescarta® (Axicabtagene Ciloleucel) or Post-Breyanzi® (Lisocabtagene Maraleucel) in Subjects With Relapsed/Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Apr 2028 ➔ Aug 2028 | Initiation date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Jul 2027 ➔ Nov 2027

Trial completion date • Trial initiation date • Trial primary completion date • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

rhIL-7-hyFc on Increasing Lymphocyte Counts in Patients With Newly Diagnosed Non-severe Lymphopenic Gliomas Following Radiation and Temozolomide (clinicaltrials.gov) - P1/2 | N=42 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jan 2032 ➔ Apr 2028

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

Efineptakin alfa (NT-I7) increases the abundance of stem-like CD8 T cells and induces tertiary lymphoid structures in lung tumors [WITHDRAWN] (ESMO-IO 2025) - No abstract available

Lung Cancer • Oncology • Solid Tumor

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=12 | Completed | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | Recruiting ➔ Completed | N=18 ➔ 12

Enrollment change • Trial completion • CNS Disorders • Rare Diseases • CD4

NeoImmuneTech announced on the 20th that it received approval from the U.S. Food and Drug Administration (FDA) for a phase 1 clinical trial plan for the combination of Janssen's BCMA CAR-T treatment 'Carvykti (ingredient: Ciltacabtagene autoleucel)' and 'NT-I7 (ingredient: epinephrine-alpha)' for patients with multiple myeloma. [Google translation] (HIT News) - "Through this study, the research team will evaluate the safety and tolerability of NT-I7 after CAR-T treatment in 40 patients with relapsed or refractory multiple myeloma, and will exploratorily confirm efficacy indicators such as complete response (CR)."

IND • New P1 trial • Multiple Myeloma

An "Off-the-Shelf" CD2 Universal CAR-T Therapy Combined with a Long-Acting IL-7 for T-Cell Malignancies (ASH 2023) - "To determine the impact of CD2 antigen loss on CAR-T cell function, CRISPR-mediated CD2 KO was performed in CD19 targeting CAR-T cells (UCART19ΔCD2). We have developed an allogenic "universal" CD2-targeting CAR-T cell UCART2, which is effective against T-ALL and CTCL/T-NHL. We found that CD2 deletion in CAR-T cells resulted in reduced secretion of effector cytokines and reduced anti-tumor activity in vivo, indicating that CD2 is critical for CAR-T function. However, when combined with rhIL-7-hyFc (efineptakin alfa), a long-acting recombinant IL-7, UCART2 induced durable complete responses in both primary and tumor rechallenge experiments in vivo."

Cutaneous T-cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CD2 • GZMB • IFNG • IL7

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

NeoImmuneTech announced phase 1 findings for its long-acting human IL-7 formulation NT-I7 (efineptakin alfa) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). (Korea Biomedical Review) - "In this study involving 17 participants, NT-I7 was administered safely, with all drug-related adverse events occurring at Grade 1 or 2 levels. Per-protocol efficacy analysis showed an objective response rate (ORR) of 87.5 percent and a complete remission (CR) rate of 75 percent."

P1 data • Diffuse Large B Cell Lymphoma

Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: NeoImmuneTech | Recruiting ➔ Completed | N=57 ➔ 17 | Trial completion date: Feb 2026 ➔ Mar 2025

Enrollment change • Trial completion • Trial completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma

NT-I7, a novel long-acting interleukin-7, promotes anti-PD-1 efficacy in an autologous humanized melanoma model. (PubMed, Sci Rep) - "We discovered a synergistic effect between NT-I7 and anti-PD-1 (Pembrolizumab) that notably augments immunotherapeutic efficacy through the expansion of TCM cells and sustained cytotoxicity. In sum, our humanized model reveals that NT-I7 holds great promise as a next-generation therapy to enhance clinical responses and patient care."

Journal • Melanoma • Oncology • Solid Tumor • IL7

Population Pharmacokinetic and Pharmacodynamic Modeling Analysis of rhIL-7-hyFc, a Hybrid Fc-Fused Long-Acting Interleukin-7, to Support Optimal Dosing Regimens in Patients with Solid Cancer. (PubMed, Drug Des Devel Ther) - P1b | "A dose range of 0.6-1.2 mg/kg administered at intervals of 6 to 12 weeks was suggested as feasible for the RP2D in further clinical trials. A population PK-PD modeling and simulation results demonstrated a strong exposure-response relationship for ALC across dosing intervals, underscoring the mechanism-based therapeutic potential of rhIL-7-hyFc in cancer immunotherapy."

Journal • PK/PD data • Oncology • Solid Tumor • IL7

Long-Acting Recombinant IL-7 (rhIL-7-hyFc) Enhances the Primary and Memory Neoantigen-Specific Immune Response to Breast Cancer Personalized Cancer Vaccines. (PubMed, Cancers (Basel)) - " We found that the combination of rhIL-7-hyFc and DNA PCV treatment prolonged neoantigen-specific CD8+ T cell responses, improved functional memory as measured based on in vivo cytotoxicity, and increased the number of neoantigen-specific tumor-infiltrating lymphocytes (TILs), resulting in improved prophylactic tumor protection and durable memory responses. Our findings support the potential of rhIL-7-hyFc to enhance the efficacy of PCVs and suggest clinical utility for adjuvant rhIL-7-hyFc in cancer immunotherapy."

Journal • Breast Cancer • Oncology • Solid Tumor • IL7

Recombinant Human IL-7 (NT-I7) in Relapsed/Refractory Multiple Myeloma Following BCMA CAR-T Therapy (Cilta-cel) (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Efineptakin alfa (NT-I7) improves overall survival and induces tertiary lymphoid structures in murine lung tumors. (PubMed, bioRxiv) - "This study demonstrates the ability of efineptakin alfa (NT-I7) to potentially augment the clinical efficacy of cancer immunotherapy by inducing tertiary lymphoid structures in the tumor microenvironment."

IO biomarker • Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • CD8 • IL7 • PD-L1

Gosha-Jinki-Gan Reduces Inflammation in Chronic Ischemic Stroke Mouse Models by Suppressing the Infiltration of Macrophages. (PubMed, Biomolecules) - "On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan's therapeutic effects on the chronic ischemic stroke."

Journal • Preclinical • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Vascular Neurology • FAP • GFAP • IL17A • IL1B • IL23A • TLR2 • TLR4 • TNFA

KEYNOTE A60: NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=215 | Completed | Sponsor: NeoImmuneTech | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • ALK • BRAF • ROS1

Phase I study of NT-I7, a long-acting interleukin-7, in severe treatment-related lymphopenia following standard radiation and temozolomide for high-grade glioma. (PubMed, Neurooncol Adv) - "Eligible HGG patients had CD4 counts <300 cells/mm3 after 5 weeks of standard chemoradiation and were receiving either ≤0.75 or ≥4 mg/day of dexamethasone. Correlative immune profiling revealed increased Ki67 expression in CD4 (P < .005) and CD8 (P < .05) after one week, along with the expansion of CD4 and CD8 T-cell subsets and CD56 + natural killer cells. NT-I7 is well tolerated and effectively increases lymphocyte and CD4 counts in severe TRL patients, regardless of glucocorticoid use, suggesting its potential to mitigate TRL and improve outcomes in HGG."

Journal • P1 data • Brain Cancer • Glioma • High Grade Glioma • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • CD4 • CD8 • IL7 • NCAM1

NeoImmuneTech, CAR-T Combination NT-I7 Repeat Administration Follow-up Clinical Trial US FDA IND Application [Google translation] (BioTimes) - "NeoImmuneTech, a global company specializing in T cell-based immunotherapy, announced on the 14th that it has submitted an investigational new drug (IND) plan for a follow-up clinical trial on the combination of NT-I7 (efineptakin alfa), a T cell booster, and CAR-T treatment to the U.S. Food and Drug Administration (FDA)....This trial, planned at the request of Dr. DiPersio, will evaluate a two-dose strategy of NT-I7 administered on days 10 and 31 after CAR-T therapy in patients with large B-cell lymphoma (LBCL) receiving Yescarta or Breyanzi. Designed as a phase 1b study to determine the additional safety associated with changing the timing and frequency of dosing, the trial plans to administer NT-I7 600 μg/kg and 720 μg/kg to up to six patients each (n=3+3)."

IND • Large B Cell Lymphoma

NT-I7 (Efineptakin Alfa), a Long-acting Human IL-7, Post-Yescarta® (Axicabtagene Ciloleucel) or Post-Breyanzi® (Lisocabtagene Maraleucel) in Subjects With Relapsed/Refractory Large B-cell Lymphoma (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1 trial • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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: May 2025 ➔ Sep 2025

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

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