Temferon (Autologous CD34+ enriched HSPCs expressing interferon-alpha 2)

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.

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.

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.

P1/2, N=27, Recruiting, Genenta Science | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and ex vivo modified with a lentiviral vector that enables HSC TEMs progeny to be loaded with IFN-a. 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/Busulfan)... 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, and anecdotal evidence for long lasting effects of Temferon in prevention of disease progression.

The results provide initial evidence of Temferon's potential to modulate the TME of GBM patients, and anecdotal evidence for long lasting effects of Temferon in prevention of disease progression.

Conclusion 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.

TEM-GBM is an ongoing open-label, Phase 1/2a dose-escalating study evaluating the safety & efficacy of Temferon in up to 21 newly diagnosed patients with glioblastoma & unmethylated MGMT promoter assigned to 7 different cohorts (3 pts each) differing by Temferon dose (0.5-4.0x106/kg) and conditioning regimen (BCNU+ or Busulfan+Thiotepa). TCR sequencing of blood and tumor samples showed a post-treatment increase in the cumulative frequency of tumor-associated T cell clones identified in 1st and 2nd surgery specimens (up to 4 out of 9 subjects). These results provide initial evidence for on-target activity of Temferon in GBM, to be consolidated with longer follow up in the higher dose cohorts.

TME characterization by scRNA and TCR sequencing is ongoing. Interim results show that Temferon is well tolerated, with no dose limiting toxicities identified to date and provide initial evidence of potential immune system activation within the TME.

Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and transduced ex vivo with a 3 rd generation lentiviral vector encoding for IFN-a2...The study evaluates safety and biological activity of Temferon in 7 cohorts of three patients each, where escalating doses of Temferon are co-administered with a fixed CD34+ cell dose of non-manipulated supporter cells following a sub-myeloablative conditioning regimen (Thiotepa + BCNU or + Busulfan)... These interim results show that Temferon is generally well tolerated by patients, with no dose limiting toxicities identified to date. The results provide initial evidence of Temferon’s potential to activate the immune system and reprogram the tumor microenvironment (TME), as predicted by preclinical studies.

Tumor microenvironment characterization by scRNA & TCR sequencing is ongoing. The results support the safety of Temferon treatment & provide early evidence of its potential to modulate the TME of GBM patients as predicted by preclinical efficacy studies.

The promising pre-clinical results obtained so far from our group led to the registration of the first drug based on this strategy, named Temferon®, which is currently in phase I/II clinical trial in our Institute for the treatment of patients with GBM. Our data also demonstrate the feasibility of inducible and intra-tumoral targeted delivery of an immune activating cytokine, thus opening the way to broader application to other cytokines and tumor types.

Four SAEs occurred in 3 patients who received Temferon (pneumonia, pulmonary embolism, febrile neutropenia, fatigue) but these events were not attributed to Temferon, resolved, & may have been related to the conditioning regimen (carmustine & thiotepa). Disease progression has been confirmed in 3 patients who received Temferon. These preliminary results indicate feasibility of engrafting a pre-determined fraction of Temferon cells in the bone marrow of GBM patients without, so far, causing dose-limiting toxicity.

Autologous HSPCs are collected by single apheresis after G-CSF/Plerixafor stimulation & used to manufacture Temferon. Conditioning occurs with carmustine 400mg/m2 at D-6 & thiotepa 5mg/kg is given twice on D-5...Conclusion These preliminary results indicate feasibility of engrafting a pre-determined fraction of Temferon cells in the BM of GBM patients, which stabilizes after D+60 & remains detectable until the latest follow up. Updated results will be presented.

Autologous HSPCs were collected by single apheresis after G-CSF/Plerixafor stimulation...Conditioning occurred with carmustine 400mg/m2 at D-6 & thiotepa 5mg/kg given twice on D-5...In summary, these preliminary results indicate feasibility of engrafting a pre-determined fraction of Temferon cells in the BM of GBM patients, which stabilizes after D+60 & remains detectable until the latest follow up. Updated results will be presented.