Temferon (Autologous CD34+ enriched HSPCs expressing interferon-alpha 2) / Genenta Science - LARVOL DELTA

Genetic Engineering of Hematopoietic Progenitor Stem Cells for Targeted IFN-α Immunotherapy Reprogramming the Solid Tumor Microenvironment: A First-in-Man Study in Glioblastoma Multiforme (NCT03866109) (ASH 2023) - P1/2 | "Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and ex vivo modified with a lentiviral vector. So far, up to 3 million Temferon cells/kg have been co-administered with a fixed dose of non-manipulated CD34+ supporter cells following a sub-myeloablative conditioning regimen (Thiotepa + BCNU or Busulfan or Busulfan alone)... These data show that Temferon is safe and biologically active at the tumor site and favors anti-tumor immunity. The results provide initial evidence of Temferon's potential to modulate the TME of GBM patients and to counteract disease progression and improve the survival of uMGMT GBM patients."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • CNS Tumor • Gene Therapies • Glioblastoma • Oncology • Solid Tumor • CD34 • CD8 • IFNA1 • MGMT • PTPRC

TEM-GU: A phase I/II clinical study of a genetically-modified Tie-2 expressing monocytes in patients with metastatic renal cell carcinoma [WITHDRAWN] (ESMO 2025) - P1/2 | "In phase 1, 12 patients receive a single Temferon infusion after busulfan conditioning. Thirty days post Temferon infusion patients without ICI exposure within 6 months receive pembrolizumab 200 mg IV, Q3W; otherwise, they receive cabozantinib 60 mg daily, orally, if disease progresses...Patients are followed for 1 year, with long-term follow-up up to 7 years. The study aims to assess tolerability, safety, and biological activity within 90 days post-Temferon (primary endpoint), and evaluate biological activity, safety, and efficacy over 1 year (secondary endpoint)."

Clinical • Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD34 • IFNA1

Genitourinary Tumor Study Ongoing with Active Screening and Enrollment (GlobeNewswire) - "In parallel, the TEM-GU Phase 1 study—designed to enroll 12 patients with genitourinary tumors—has begun recruitment....Genenta aims to demonstrate the safety and tolerability of Temferon in patients with Metastatic Renal Cell Carcinoma by year-end."

Enrollment open • P1/2 data • Clear Cell Renal Cell Carcinoma

Genenta Announces Long-Term Follow-Up Observations in Brain Tumor (GBM) Study with Emerging Survival Signals (GlobeNewswire) - P1/2a | N=27 | TEM-GBM (NCT03866109) | Sponsor: Genenta Science | "Genenta Science...announced that a total of 38 patients were enrolled in newly diagnosed glioblastoma multiforme (TEM-GBM) study, with 25 patients receiving Temferon. Two patients have been enrolled in the TEM-LT long-term follow-up study, surviving three years from the time of 1st surgery. One of these long-term survivors has not experienced disease progression following Temferon administration and has not required any second-line therapies. The other showed initial signs of disease progression that subsequently stabilized without additional therapeutic intervention. As of the April data cutoff, the survival rate at two years in the GBM trial for unmethylated MGMT (uMGMT) patients remained consistent at 29% with median overall survival holding steady at 17 months."

Enrollment status • P1/2 data • Glioblastoma

Genenta Announces €20 million ($21.9M) Financing To Expand Pipeline As Brain Tumor Trial Is Showing Promising Survival Rates (GlobeNewswire) - "Genenta Science...today announced a €20 million ($21.9 million) financing through the issuance of a Mandatory Convertible Bond to ENEA Tech and Biomedical (ETB) to support the expansion of its pipeline by advancing Temferon in metastatic Renal Cell Cancer (mRCC)....The bond will not result in immediate dilution to Genenta's shareholders, and is expected to provide the necessary capital to achieve key milestones in the Company's new mRCC trial."

Financing • Renal Cell Carcinoma

Phase 1/2a Glioblastoma Multiforme (GBM) uMGMT trial (GlobeNewswire) - P1/2a | NCT03866109 | Sponsor: Genenta Science | "The February data cutoff from the Phase 1/2a Glioblastoma Multiforme (GBM) uMGMT trial shows an increase in the percentage of patients surviving at two years, now reaching 29%, compared to 25% in October. Additionally, there is a marginal improvement in median overall survival, which now stands at 17 months. Historically reported data showed the overall survival of uMGMT patients undergoing standard of care to be approximately 14% at two years with a median overall survival of 13–15 months."

P1/2 data • Glioblastoma

TEM-GBM: A Study Evaluating Temferon in Patients with Glioblastoma & Unmethylated MGMT (clinicaltrials.gov) - P1/2 | N=27 | Recruiting | Sponsor: Genenta Science | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2025

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

TEM-GU: A Clinical Gene Therapy Study with Hematopoietic Stem Cells for the Treatment, with Single Dose of Temferon, of Patients Suffering from Metastatic Renal Cell Carcinoma (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: Genenta Science

Gene therapy • Metastases • New P1/2 trial • Clear Cell Renal Cell Carcinoma • Gene Therapies • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Median and 2 years survival of newly diagnosed unmethylated MGMT glioblastoma patients treated with Temferon immuno-gene therapy (SNO 2024) - "The other four patients instead received a 2nd treatment line (bevacizumab, regorafenib, Gamma-Knife, metronomic Temozolomide, Lomustine) as per the PI judgment, on average after 443 days from 1st surgery (333 days from Temefron - range 223-1030 days from first surgery). Specifically, Bevacizumab administration started 12 months after 1st surgery for one patient and 19 months for the other 2 patients at 5 mg/kg. The data further confirms the initial evidence on safety and tolerability of Temferon and highlight the potential to prolong the survival of patients affected by uMGMT GBM."

Clinical • Gene therapy • Brain Cancer • CNS Tumor • Gene Therapies • Glioblastoma • Oncology • Solid Tumor • IFNA1

Genenta Secures Approval for Innovative Trial for Metastatic Renal Cell Cancer (GlobeNewswire) - "Genenta Science...is pleased to announce that the Agenzia Italiana del Farmaco (AIFA) has approved a new Phase 1 clinical trial for metastatic Renal Cell Cancer (mRCC), marking a significant expansion of the potential applications for Genenta’s flagship product, Temferon....The newly approved mRCC trial, expected to commence in Q4 2024, targets a high-risk patient population whose median overall survival is currently less than 2 years after multiple lines of therapy."

New P1 trial • Renal Cell Carcinoma

Macrophage derived immunotherapy in glioblastoma: Phase I TEM-GBM-001 results (ESMO 2024) - P1/2 | "These data corroborate the initial evidence on the safety and tolerability of Temferon and the potential to reprogram GBM TME and elicit T cell-mediated immune responses."

IO biomarker • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD34 • IFNA1 • PTPRC

Single cell analysis of the glioblastoma microenvironment in patients transplanted with hematopoietic stem cells engineered with a tumor‐selective interferon‐alpha cassette (ESGCT 2023) - P1/2 | "Intra-population differential gene expression analysis, followed by Gene Set Enrichment Analysis showed strong up-regulation of IFN-a and inflammatory responses in most of the clusters from myeloid and T cells, but also CD45- tumor and stromal cell compartments from Temferon patients suggesting pervasive IFN-a payload delivery into the GBM TME. These data indicate recruitment and integration of Temferon progeny into the TME, where they locally release IFN-a and reprogram the myeloid and lymphoid TME."

Clinical • Brain Cancer • CNS Tumor • Gene Therapies • Glioblastoma • Oncology • Solid Tumor • Transplantation • CD8 • PTPRC

Reprogramming of the Tumor Microenvironment in Glioblastoma Multiforme by Transplantation of Genetically-Engineered Hematopoietic Stem Cells (ASGCT 2024) - P1/2 | "Temferon, a first-in-class gene therapy targeting the myeloid TME in GBM patients is safe and biologically active at the tumor site favoring anti-tumor immunity. Preliminary survival data are promising, but longer follow-up is needed."

Biomarker • IO biomarker • Tumor microenvironment • Brain Cancer • CNS Tumor • Gene Therapies • Glioblastoma • Hematological Malignancies • Oncology • Solid Tumor • Transplantation • CD8 • IFNA1

A MACROPHAGES-BASED IMMUNOTHERAPY OF SOLID TUMORS MICROENVIRONMENT: PRELIMINARY RESULTS OF THE TEM-GBM_01 STUDY (EBMT 2024) - P1/2 | "Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and ex vivo modified with a lentiviral vector. Following a sub-myeloablative conditioning regimen (Thiotepa + BCNU or Thiotepa + Busulfan or Busulfan alone), up to 3 million Temferon cells/kg are administered following a fixed dose of non-manipulated CD34+ supporter cells As of 27th July 2023, 21 GBM patients in 7 cohorts received incremental doses of Temferon up to 3 million cells/kg and 5 patients were still alive with a median OS of 17 months and a median PFS of 8.3 months following initial surgery... These data corroborate the initial evidence on safety and tolerability of Temferon. They also suggest that Temferon has potential to counteract disease progression in patients affected by unmethylated MGMT GBM"

IO biomarker • Brain Cancer • CNS Tumor • Febrile Neutropenia • Glioblastoma • Glioma • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • Transplantation • CD34 • IFNA1 • MGMT

Genenta Demonstrated Reprogramming of the Tumor Microenvironment in GBM Patients, Paving the Way for Innovative Treatments of Solid Tumors (GlobeNewswire) - "Genenta Science...have successfully dosed the first of three patients in Cohort 8 (Temferon at 4x10^6/kg), the last cohort of the Phase 1 dose-ranging part of the Phase 1/2 clinical trial in newly diagnosed uMGMT Glioblastoma Multiforme (TEM-GBM) patients. The second patient has been enrolled and the treatment is planned....We expect reporting top line Phase 1 dose-ranging data by the end of 2Q24."

P1 data • Trial status • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Impact on survival of interferon-alpha delivery in glioblastoma with unmethylated MGMT by immuno-gene therapy with Temferon (SNO 2023) - "The other four patients with 2 year follow-up were treated with Gamma-Knife followed by bevacizumab (n = 1), regorafenib followed by bevacizumab (n = 1) and bevacizumab only (n = 2). These data corroborate the initial evidence on safety and tolerability of Temferon. They also suggest that Temferon has potential to counteract disease progression in patients affected by uMGMT GBM."

Gene therapy • Brain Cancer • CNS Tumor • Gene Therapies • Glioblastoma • Oncology • Solid Tumor • IFNA1

Intra-tumor delivery of IFN-alpha by Tie-2 transduced monocytes associated with favorable 2-year survival in unmethylated MGMT GBM patients: preliminary results of TEM-GBM phase 1/2a study (SITC 2023) - P1/2 | "Temferon is administered by ASCT after the RTx treatment without the concurrent administration of Temozolomide, whose survival benefit is known to be marginal in the uMGMT population. One out of the surviving patients was enrolled in a long-term follow-up study and survived up to 3 years after surgery without any 2nd-line therapy added for 2 years. Conclusions These data provide initial evidence on Temferon potential to counteract disease progression and improve the survival of uMGMT GBM patients."

Clinical • IO biomarker • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • IFNA1

MACROPHAGES-BASED IMMUNOTHERAPY OF SOLID TUMORS MICROENVIRONMENT: THE TEM-GBM STUDY (NCT03866109) (EANO 2023) - P1/2 | "The comparison of the overall ISGs expression at first surgery and second surgery highlighted the activation of IFN-responsive genes at second surgery suggesting the occurrence of the local delivery within the TME of biologically active IFN-a. CONCLUSION The results provide initial evidence of Temferon’s potential to modulate the TME of GBM patients."

IO biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Hematological Malignancies • Oncology • Solid Tumor • IFIT1 • IRF7 • PTPRC

Tumor-restricted delivery of an immune-therapeutic payload by modified macrophages for the treatment of glioblastoma: The TEM-GBM STUDY (NCT03866109) (ESMO 2023) - P1/2 | "The frequency of peripherally expanded clones found in the tumor samples increases by the second surgery, as evidence of a notable crosstalk between the peripheral and tumor repertoires of T cells. Conclusions The results provide initial evidence of Temferon's potential to reprogram GBM TME and elicit T cell-mediated immune responses."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IFNA1

Genenta Announces Ongoing Clinical Trial Progress and Proposed Expansion in Solid Tumor Treatments (GlobeNewswire) - "Genenta Science...announced that: the Phase 1 dose-ranging clinical trial in Glioblastoma Multiforme (TEM-GBM) is progressing in line with the development program....We have selected Refractory Advanced Genitourinary Malignancies including Renal Cell Cancer (RCC) as the second solid tumor indication for Temferon. Late-stage RCC is considered an orphan disease with an unfavorable prognosis for Stage IV RCC patients."

Trial status • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Glioma • Oncology • Renal Cell Carcinoma • Solid Tumor

The European Commission Grants Orphan Drug Designation to Temferon for Treatment of Glioma (GlobeNewswire) - "Genenta Science...today announced that the European Commission has granted Orphan Drug Designation (ODD) to Temferon™ for the treatment of glioma."

European regulatory • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Genenta to Provide Update on Lead Product Temferon (GlobeNewswire) - "Luigi Naldini...will be presenting the company cell-based platform harnessing the power of hematopoietic stem cells to provide durable, safe, and well tolerated treatment for solid tumors at several upcoming scientific congresses. Prof. Luigi Naldini will provide updates on the efficacy of Genenta's lead product candidate, Temferon, in pre-clinical solid tumor models and preliminary clinical biological data confirming in patients at these congresses. From pre-clinical experiments, it has been observed that Temferon allows the immune system to see the tumor and mount an effective immune response."

Clinical data • Preclinical • Oncology • Solid Tumor

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[VIRTUAL] A PHASE I-IIA STUDY OF GENETICALLY MODIFIED TIE-2 EXPRESSING MONOCYTES IN PATIENTS WITH GLIOBLASTOMA MULTIFORME (TEM-GBM STUDY) (EHA 2021) - "Conclusion Our interim results show that Temferon is well tolerated by patients, with no dose limiting toxicities identified to date. The results provide initial evidence of Temferon potential to modulate the TME of GBM patients, as predicted by preclinical studies."

Clinical • IO biomarker • P1/2 data • Bone Marrow Transplantation • Brain Cancer • Cardiovascular • CNS Disorders • Glioblastoma • Hematological Disorders • Infectious Disease • Oncology • Solid Tumor • Transplantation • Venous Thromboembolism • MRI

Harnessing genetically engineered hematopoietic progenitor cells to redirect the tumor immune microenvironment against glioblastoma (TEM-GBM Study). (ASCO 2022) - P1/2 | "Our interim results show that Temferon is well tolerated, with no dose limiting toxicities identified to date. The results provide initial evidence of Temferon’s potential to modulate the TME of GBM patients."

IO biomarker • Brain Cancer • CNS Disorders • Epilepsy • Glioblastoma • Immunology • Infectious Disease • Oncology • Solid Tumor • IFNA1 • PTPRC