Genenta Science has reported encouraging long-term survival data from its phase 1/2a TEM-GBM trial, with two patients with newly diagnosed glioblastoma multiforme surviving three years from the time of initial surgery following treatment with Temferon, the company's investigational hematopoietic stem cell therapy.
Long-Term Survival Signals Emerge
Of the 38 patients enrolled in the TEM-GBM study, 25 received Temferon treatment. Two patients have now been enrolled in the TEM-LT long-term follow-up study after demonstrating exceptional survival outcomes. One patient has not experienced disease progression following Temferon administration and has not required any second-line therapies. The second patient showed initial signs of disease progression that subsequently stabilized without additional therapeutic intervention.
"Both these cases suggest possible Temferon-mediated control of disease progression, which warrants further investigation in larger studies," Genenta stated in its announcement.
Improved Survival Metrics in Challenging Patient Population
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. These outcomes represent a meaningful improvement over historical data, where uMGMT patients receiving standard of care have shown a two-year survival rate of approximately 14% and a median overall survival of 13 to 15 months.
The unmethylated MGMT patient population represents a particularly challenging subset of glioblastoma patients with historically poor prognosis, making these survival improvements clinically significant.
Novel Mechanism of Action
Temferon is an investigational, cell-based gene therapy composed of autologous CD34-positive, enriched hematopoietic stem and progenitor cells that have been transduced ex vivo with a lentiviral vector encoding myeloid-specific interferon-alpha2 expression. The therapy's mechanism of action is based on reprogramming the tumor microenvironment, which promotes the activation and durability of adaptive immune responses.
"For the first time, we show that hematopoietic stem cells can be engineered to durably give rise to myeloid cells that localize to the tumor and reprogram its immune environment," said Luigi Naldini, co-founder of Genenta Science and professor at San Raffaele University School of Medicine. "In glioblastoma, this strategy induced a pro-inflammatory shift in macrophages and the emergence of tumor-reactive T cells, offering a promising new avenue for immune engagement against one of the most resistant cancers."
Expansion into Genitourinary Cancers
Genenta has initiated recruitment for the TEM-GU Phase 1 study, designed to enroll 12 patients with genitourinary tumors. In this trial, Temferon is administered at a fixed dose of 4 million genetically modified cells per kilogram of body weight—a level previously shown to be safe and well tolerated in the TEM-GBM dose-ranging study.
The company aims to demonstrate the safety and tolerability of Temferon in patients with metastatic renal cell carcinoma by year-end. The study is designed to evaluate Temferon in combination with immune checkpoint inhibitors or tyrosine kinase inhibitors to assess the potential for immunologic synergy in this patient population.
Scientific Validation and Future Prospects
A scientific manuscript demonstrating Temferon's potential to enhance and prolong the durability of CAR-T activity in preclinical murine models of solid tumors has been accepted for publication in Science Translational Medicine, providing additional scientific validation for the platform's mechanism.
"We are encouraged by the consistent clinical signals emerging from our glioblastoma trial," said Pierluigi Paracchi, CEO of Genenta Science. "These findings reinforce our confidence in Temferon's differentiated mechanism and support our commitment to advancing the platform."
Temferon has previously received orphan drug designation for the treatment of patients with glioma and glioblastoma multiforme in the European Union, and glioblastoma multiforme in the United States, highlighting the significant unmet medical need in this patient population.
