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

Efineptakin alfa (NT-I7) improves overall survival and induces immune niches in murine tumors. (PubMed, Genes Dis) - "Spatial transcriptomic analyses of the TME further demonstrated that the immune aggregates induced by NT-I7 included TLS-like structures with enrichment of Cd274 (PD-L1) transcripts and genes involved in antigen processing and presentation. Up-regulation of Cd274 in the TLS-like structures may provide opportunities for synergy between NT-I7 and PD-1-targeted immunotherapy."

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

Tolerance Bio, Inc....announced an exclusive license agreement with NeoImmuneTech (NIT, KOSDAQ: 950220.KQ) for the development and commercialization of efineptakin alfa (also known as NT-I7), a clinical-stage long-acting IL-7 fusion protein, for certain thymus-related indications in the Americas and Europe. (Businesswire) - "The agreement marks Tolerance Bio’s transition to a clinical-stage biotechnology company. The Company is targeting initiation of Phase 2 clinical trials to evaluate efineptakin alfa in the enhancement of thymic function...Under the terms of the agreement, the license includes potential development and sales milestone payments of up to $260 million, as well as equity consideration and tiered royalties on net sales....Tolerance Bio plans to advance efineptakin alfa in new indications aligned with its strategy to preserve thymic T cell output and enhance immune resilience in immunologically vulnerable populations."

Licensing / partnership • New P2 trial • Immunology

NT-I7 in Combination With Atezolizumab in Previously Untreated, PD-L1-expressing, Locally Advanced or Metastatic NSCLC (clinicaltrials.gov) - P2 | N=33 | Terminated | Sponsor: NeoImmuneTech | N=83 ➔ 33 | Active, not recruiting ➔ Terminated; sponsor decision (not for safety)

Enrollment change • Trial termination • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

TRINITY: HPV 16-positive and/or HPV 18-positive Recurrent and/or For Patients With Metastatic Head and Neck Cancer to Evaluate GX-188E DNA Vaccination, GX-I7 and Nivolumab Combination Therapy (clinicaltrials.gov) - P2 | N=21 | Active, not recruiting | Sponsor: Yonsei University | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2026 ➔ Jan 2027 | Trial primary completion date: Mar 2026 ➔ Jan 2027

Enrollment closed • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Recombinant Human IL-7 (NT-I7) in Relapsed/Refractory Multiple Myeloma Following BCMA CAR-T Therapy (Cilta-cel) (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Effect of IL7 on ImmTAC-mediated killing by T cells in vitro and T-cell fitness in patients. (ASCO 2026) - P1/2, P2 | "Funded by Immunocore Ltd Background: A blood T cell fitness (TCF) signature, reflecting properties of naïve and stem cell memory T cells, was strongly associated with clinical benefit from tebentafusp (gp100 × CD3) and brenetafusp (PRAME × CD3) ImmTAC bispecific therapies¹...The proportion of TCF high patients increased from 36% at baseline to 93% post NTI7 monotherapy... Despite repeated antigen stimulation in vitro, IL7 sustained naïve/memory T cells, enhanced ImmTAC‑redirected T cell cytotoxicity and IFNγ production, and reduced T cell exhaustion. A single dose of rhIL7 resulted in a sustained increase in TCF signature and converted patients with low TCF signature into high TCF. These findings support combination with IL7 as a rational strategy to augment T cell fitness and potentially improve efficacy of ImmTAC bispecific T cell therapies."

Preclinical • Breast Cancer • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Uveal Melanoma • CD28 • GPR183 • IFNG • IL7 • IL7R • LXN • PRAME

Long-acting IL-7 restores T-cell reconstitution in a humanized mouse model of lymphopenia. (PubMed, J Allergy Clin Immunol) - "A single dose of NT-I7 restored T-cell numbers in a mouse model of ICL and improved lymphocyte counts in a single-patient study."

IO biomarker • Journal • Preclinical • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Oncology • CD4 • CD8 • IL7

Neoadjuvant pembrolizumab with therapeutic DNA vaccine reshape intratumoral immunity in a phase 2 trial of HPV-positive HNSCC (AACR 2026) - "Guided by these results, we conducted a phase 2 neoadjuvant trial combining pembrolizumab, HPV DNA vaccine (GX-188E), and long-acting IL-7 (GX-I7) in patients with resectable HPV-positive HNSCC. Analyses of independent HPV-positive HNSCC cohorts aligned with these observations, showing that tumors enriched for GZMK-programmed CD8⁺ states exhibit stronger antitumor immunity and improved long-term outcomes. Taken together, these comprehensive preclinical, clinical, and exploratory analyses reveal that IL-7 amplifies a GZMK⁺ effector-memory CD8⁺ T-cell program driving sustained recirculation, diversification, and renewal of tumor-reactive CD8⁺ T cells, highlighting a mechanistic axis with potential to enhance the durability of cancer vaccine responses."

Clinical • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • GZMK • IL7 • IL7R • STAT5

Long-Acting IL-7 (NT-I7) as an Immune Reconstitution Strategy in PML: Immunological and Clinical Outcomes from a Pilot Study (AAN 2026) - "The modest impact on PML survival underscores challenges related to advanced disease, pre-treatment immune repertoire and toxicities influenced by underlying disease. This study provides key insights into IL-7–driven immune reconstitution that will guide future optimization of IL-7–based therapeutic strategies."

Clinical • Clinical data • Late-breaking abstract • CNS Disorders • Hematological Malignancies • Infectious Disease • Rare Diseases • CD4 • CD8 • IL7

Long-acting IL-7 induces distinct transcriptomic features in peripheral T cells of patients with solid tumors. (PubMed, JCI Insight) - P1b | "Our results demonstrate that rhIL-7-hyFc induces robust peripheral T-cell expansion and activation in patients with solid tumors, supporting its potential use for lymphopenic patients treated with cancer immunotherapy."

Journal • Oncology • Solid Tumor • IL7 • IL7R • MYC • PIM1 • STAT5

Recombinant Human IL-7 (NT-I7) in Relapsed/Refractory Multiple Myeloma Following BCMA CAR-T Therapy (Cilta-cel) (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: Washington University School of Medicine | N=40 ➔ 52

Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

rhIL-7-hyFc (efineptakin-alfa, NT-I7) increases tumor-specific CD8+ T cells despite FOLFOX cytotoxicity effect (AACR 2024) - "FOLFOX is a chemotherapy regimen composed of 5-fluorouracil, leucovorin, and oxaliplatin that inhibits DNA duplication and eradicates rapidly dividing cells (3). However, adding FOLFOX does not affect the NT-I7-driven increase of tumor-specific CD8+ T cells within the tumor. Taken together, our data demonstrate that FOLFOX does not compromise NT-I7's ability to increase tumor-specific T cells within the tumor and the combination enhances the anti-tumor response irrespective of the timing of NT-I7 administration."

Oncology • CD8 • IL7

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

Expansion and mobilization of virus-specific stem-like CD8 T cells in chronic viral infection after treatment with a long-acting IL-7, NT-I7. (PubMed, Cell Rep) - "NT-I7 treatment led to an increase in stem-like CD8 T cells in circulation and peripheral tissues, contrasting with their resident property in lymphoid organs. These findings suggest NT-I7 as a promising strategy to expand and mobilize stem-like CD8 T cells to enhance antiviral and anticancer immunotherapies."

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

NT-I7, a long-acting interleukin-7, increases lymphocyte counts and induces CD8+ T cell clonotype expansion in patients with newly diagnosed high-grade gliomas. (PubMed, Clin Cancer Res) - P1/2 | "NT-I7 has the potential to maintain and increase lymphocyte counts in HGG patients and warrants further investigation, particularly in combination with immune-based therapies."

Journal • Brain Cancer • Glioblastoma • Glioma • High Grade Glioma • Oncology • Solid Tumor • CD4 • CD8 • CXCL9 • IL7 • MGMT

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 | Trial completion date: Jul 2028 ➔ Nov 2028 | Initiation date: Jan 2026 ➔ May 2026 | Trial primary completion date: Oct 2027 ➔ Feb 2028

Trial completion date • Trial initiation date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Long-acting interleukin-7 improves the efficacy of oncolytic viral therapy in glioblastoma. (PubMed, Nat Commun) - "To overcome these challenges, here we develop a treatment strategy we term "expand and pull," which uses systemic administration of rhIL-7-hyFc, a long-acting recombinant human interleukin-7, to increase peripheral T cell abundance ("expand"), followed by intratumoral oncolytic virus treatment to recruit these cells to the tumor microenvironment ("pull")...We observe similar survival efficacy in experiments using a safer, genetically modified Δ10 3'-UTR ZIKV, as well as the clinically tested oncolytic adenovirus, Delta24-RGD. Collectively, our findings demonstrate that augmentation of both the systemic and local immune responses improves the utility of GBM-targeted immunotherapies."

IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Infectious Disease • Oncology • Solid Tumor • IL7

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

Enrollment open • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma

GENUINE: Trial of the Combination of GX-188E Vaccination, GX-I7 and Pembrolizumab in Patients With Advanced, Resectable HPV Type 16 and/or 18 Positive Head and Neck Cancer (clinicaltrials.gov) - P2 | N=56 | Active, not recruiting | Sponsor: Yonsei University | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Aug 2025 ➔ Oct 2026

Enrollment closed • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

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