pharma · Acute myeloid leukemia · Juvenile idiopathic arthritis
Istituto Gentili S.r.l.
Istituto Gentili S.r.l is a pharma organization headquartered in MILANO, IT. Primary therapeutic focus areas include Acute myeloid leukemia, Juvenile idiopathic arthritis, Malignant Pleural Mesothelioma, Osteogenesis Imp
Phase 2 · small molecule · Glioblastoma
Temozolomide SUN is an oral small-molecule antineoplastic agent developed by Istituto Gentili S.r.l. for glioblastoma, currently in Phase 2 development under the trial designation IRST191.05 (NCT 2024-512493-98-00). The program combines temozolomide with a dendritic cell vaccine (DC-VACCINE_IRSTIRCCS) in a study titled
Internal code IRST191.05
Temozolomide SUN is an oral small-molecule antineoplastic agent developed by Istituto Gentili S.r.l. for glioblastoma, currently in Phase 2 development under the trial designation IRST191.05 (NCT 2024-512493-98-00). The program combines temozolomide with a dendritic cell vaccine (DC-VACCINE_IRSTIRCCS) in a study titled 'Vaccination with Autologous Dendritic cells loaded with Autologous Tumour homogenate in Glioblastoma: a phase II Study (Combi G-Vax).' Temozolomide itself is a well-established alkylating agent with multiple approved formulations globally; however, this investigational program explores combination immunotherapy to enhance efficacy in glioblastoma. The sponsor is advancing the combination approach as an active Phase 2 program. Regulatory approvals for temozolomide monotherapy exist across major markets including the United States, European Union, Australia, and China, with multiple manufacturers holding approvals. The current program's focus on combination therapy with autologous dendritic cells represents a strategy to improve outcomes in this highly aggressive brain tumor indication.
Glioblastoma remains one of the most lethal human malignancies, with median overall survival of approximately 12–15 months despite standard-of-care temozolomide and radiation therapy. The unmet medical need is substantial: current treatments offer limited durable responses, and resistance mechanisms frequently emerge. This investigational program addresses the need for improved therapeutic strategies by combining a standard chemotherapy backbone (temozolomide) with personalized dendritic cell immunotherapy, potentially leveraging both cytotoxic and immune-mediated mechanisms. The market relevance is high given glioblastoma's poor prognosis and the limited number of effective treatment options beyond standard chemoradiation. Competitive positioning is notable because most approved glioblastoma therapies rely on chemotherapy or targeted agents; immunotherapy combinations remain an active area of investigation. The patient population is relatively small but critically underserved, with high mortality rates driving demand for novel approaches. Commercial significance is moderate to substantial if the combination demonstrates superior efficacy, as glioblastoma patients represent a high-value population willing to pursue investigational therapies with potential survival benefit.
Drug Class: Antineoplastic and immunomodulating agents (L01 therapeutic class)
Modality: Small-molecule alkylating agent combined with autologous dendritic cell vaccine
Route of Administration: Oral (temozolomide component available in 5 mg, 20 mg, 100 mg, and 250 mg hard capsules)
Mechanism of Action: Temozolomide acts as an alkylating agent causing DNA cross-linking and strand breaks; the dendritic cell vaccine component (DC-VACCINE_IRSTIRCCS) is designed to provide personalized immunotherapy using autologous dendritic cells loaded with autologous tumor homogenate to elicit anti-tumor immune responses
Related Therapies: Temozolomide monotherapy is standard-of-care in glioblastoma; other approved agents include bevacizumab (anti-VEGF) and various targeted therapies
First Approval (Temozolomide Monotherapy): Approved in multiple jurisdictions; earliest listed date in Australia: 2000-02-01
Patent Status: Not yet disclosed for this specific combination program
Also known as: GBM, GBM (glioblastoma), WHO grade IV glioma, glioblastoma (disease), glioblastoma multiforme, glioblastoma multiforme (disease)
Prevalence: Point prevalence: 1-9 / 100 000 (Worldwide) — source: Orphanet, validated.
The most malignant astrocytic tumor (WHO grade IV). It is composed of poorly differentiated neoplastic astrocytes and it is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. It may develop from diffuse astrocytoma WHO grade II or anaplastic astrocytoma (secondary glioblastoma, IDH-mutant), but more frequently, it manifests after a short clinical history de novo, without evidence of a less malignant precursor lesion (primary glioblastoma, IDH- wildtype). (Adapted from WHO)
ClinicalTrials.gov lists 877 registered studies for Glioblastoma (AACT aggregate).
Phase breakdown: NA (252), PHASE2 (223), PHASE1 (206), PHASE1/PHASE2 (86), EARLY_PHASE1 (49), PHASE3 (45), PHASE2/PHASE3 (11), PHASE4 (5)
Common investigational therapies:
Disease data sourced from MONDO Disease Ontology (MONDO:0018177), Orphanet — glioblastoma, NCT00001148, NCT00001171, NCT00009035, NCT00028158, NCT00029783, AACT (ClinicalTrials.gov aggregate), ClinicalTrials.gov, Open Targets Platform (CC BY 4.0).
Combi G-Vax Phase 2 Active
Phase 2 study 'Vaccination with Autologous Dendritic cells loaded with Autologous Tumour homogenate in Glioblastoma: a phase II Study (Combi G-Vax)' is currently active under NCT 2024-512493-98-00.
The competitive landscape for glioblastoma therapy includes multiple approved agents, though the facts provided list competitors that span oncology broadly rather than glioblastoma-specific therapies. Approved temozolomide manufacturers in the EU include Accord Healthcare S.L.U., Hexal AG, Merck Sharp & Dohme B.V., ORPHELIA Pharma, Sandoz GmbH, Sun Pharmaceutical Industries Europe B.V., Teva B.V., and medac Gesellschaft für klinische Spezialprodukte mbH. In the United States, temozolomide is available from multiple generic and branded manufacturers including Accord Healthcare, Amneal Pharmaceuticals, ANI Pharmaceuticals, Apotex, Merck Sharp Dohme, and Sun Pharma. The original branded product (Temodal) is marketed by Merck Sharp & Dohme. The investigational Combi G-Vax program differentiates itself by combining chemotherapy with personalized immunotherapy, a strategy distinct from monotherapy temozolomide or other single-agent approved glioblastoma treatments. Direct competitors in the glioblastoma immunotherapy space are not explicitly identified in the provided facts, limiting detailed competitive positioning analysis.
| Therapy | Company | Mechanism | Status |
|---|---|---|---|
| PFIZER AUSTRALIA PTY LTD | Pfizer Australia Pty Ltd | — | approved |
| IMBRUVICA | Janssen-Cilag Pty Ltd | — | approved |
| AFINITOR | Novartis Pharmaceuticals | — | approved |
| LYSODREN | S.A. | — | approved |
| INLYTA | Pfizer Australia Pty Ltd | — | approved |
| LYNOZYFIC | Regeneron UK Limited | — | approved |
| VYXEOS LIPOSOMAL (PREVIOUSLY VYXEOS) | Jazz Pharmaceuticals Ireland Limited | — | approved |
| KYPROLIS | Amgen | — | approved |
| UNITUXIN | United Therapeutics Europe Ltd | — | approved |
| PACLITAXEL ACCORD | Accord Healthcare Pty. | — | approved |
| OFEV | Boehringer Ingelheim Pty Ltd | — | approved |
| ARX-IMATINIB | Alphapharm Pty Ltd | — | approved |
| CARMUSTINE | — | Glutathione reductase inhibitor | Approved |
| BEVACIZUMAB | — | Vascular endothelial growth factor A inhibitor | Approved |
| TRABEDERSEN | — | Transforming growth factor beta-2 mRNA antisense inhibitor | Phase 3 |
| TOFACITINIB | — | Janus Kinase (JAK) inhibitor | Phase 3 |
| RINDOPEPIMUT | — | Epidermal growth factor receptor erbB1 vaccine antigen | Phase 3 |
| OMBIPEPIMUT-S | — | Wilms tumor protein vaccine antigen | Phase 3 |
| NIVOLUMAB | — | Programmed cell death protein 1 inhibitor | Phase 3 |
| NIMOTUZUMAB | — | Epidermal growth factor receptor erbB1 inhibitor | Phase 3 |
Additional associated therapies sourced from Open Targets Platform (CC0), linked to NovaPharmaNews drug profiles where matched.
United States: Temozolomide is approved via multiple ANDA applications (ANDA078879, ANDA201528, ANDA201742, ANDA203490, ANDA203691, ANDA203898, ANDA203959, ANDA204159, ANDA204639, ANDA205227, ANDA206309, ANDA206413, ANDA206750, ANDA207658, ANDA210030, ANDA213328) and NDA applications (NDA021029, NDA022277). The investigational Combi G-Vax program status in the US is not yet disclosed.
European Union: Temozolomide is approved with multiple EMA product numbers (EMEA/H/C/000229, EMEA/H/C/001124, EMEA/H/C/001125, EMEA/H/C/001126, EMEA/H/C/001127, EMEA/H/C/001128, EMEA/H/C/002198, EMEA/H/C/006169) from multiple marketing authorization holders. Authorisation dates include 02/05/2025, 06/11/2025, and 10/07/2025. The Combi G-Vax program regulatory status in the EU is not yet disclosed.
Australia: Temozolomide is approved with PBS codes (10062N, 2438H, 8378Y, 8379B, 8380C, 8381D, 8819E, 8820F, 8821G, 9361Q) from multiple sponsors including Alphapharm Pty Ltd, Apotex Pty Ltd, Juno Pharmaceuticals Pty Ltd, and Merck Sharp & Dohme (Australia) Pty Ltd. First listed dates: 2000-02-01, 2005-06-01, 2009-01-01. The Combi G-Vax program regulatory status in Australia is not yet disclosed.
China: Temozolomide is in clinical trials (NCT05457829). The Combi G-Vax program regulatory status in China is not yet disclosed.
Japan (PMDA): Regulatory status not yet disclosed.
Temozolomide SUN is being investigated for glioblastoma in a Phase 2 combination study (Combi G-Vax) that pairs temozolomide with autologous dendritic cell vaccine. Temozolomide monotherapy is approved for glioblastoma and other malignancies.
Temozolomide as a monotherapy is FDA-approved via multiple ANDA and NDA applications. The investigational Combi G-Vax combination program has not yet received FDA approval and remains in Phase 2 development.
Temozolomide is an alkylating agent that causes DNA cross-linking and strand breaks. In the Combi G-Vax program, it is combined with autologous dendritic cells loaded with tumor homogenate to provide both chemotherapy and personalized immunotherapy.
Sun Pharmaceutical Industries Europe B.V. is listed as a marketing authorization holder for temozolomide in the EU. Istituto Gentili S.r.l. is the sponsor of the investigational Combi G-Vax program.
The indication is glioblastoma, one of the most aggressive primary brain tumors with poor prognosis and limited treatment options.
The investigational Combi G-Vax program is in Phase 2 development. Temozolomide monotherapy is approved in multiple markets.
The trial is registered as NCT 2024-512493-98-00 and is designated IRST191.05 internally.
Yes, temozolomide is approved in the European Union with multiple EMA product numbers and marketing authorization holders including Accord Healthcare, Hexal AG, Merck Sharp & Dohme, and others.
Yes, temozolomide is approved in Australia with PBS codes and is marketed by multiple sponsors including Alphapharm Pty Ltd, Apotex Pty Ltd, and Merck Sharp & Dohme (Australia) Pty Ltd.
Temozolomide SUN is administered orally as hard capsules available in 5 mg, 20 mg, 100 mg, and 250 mg strengths.
The DC-VACCINE_IRSTIRCCS component uses autologous dendritic cells loaded with autologous tumor homogenate to elicit personalized anti-tumor immune responses, complementing the chemotherapy effect of temozolomide.
Glioblastoma has a median overall survival of approximately 12–15 months despite standard-of-care temozolomide and radiation therapy, with limited durable responses and frequent resistance, creating substantial need for improved therapies.
Temozolomide was first listed in Australia on 2000-02-01. It has since been approved in the United States, European Union, and other major markets.
Multiple manufacturers produce temozolomide, including at least 8 EU marketing authorization holders, 17 US manufacturers, and several in Australia and other regions.
Temozolomide is classified as an antineoplastic and immunomodulating agent (L01 therapeutic class).
No partner is disclosed for the Combi G-Vax program; Istituto Gentili S.r.l. is listed as the sole sponsor.
IRST191.05 → Drug → Target → Indication → Company → Trials → Competitors
Strategic Implications: Istituto Gentili's approach of combining established chemotherapy (temozolomide) with personalized dendritic cell immunotherapy reflects a broader industry trend toward combination oncology strategies. This strategy leverages the known efficacy of temozolomide while attempting to overcome resistance through immune activation, potentially addressing the high unmet need in glioblastoma.
Competitive Implications: The program does not directly compete with temozolomide monotherapy manufacturers, as it represents a novel combination. However, it competes conceptually with other investigational glioblastoma immunotherapies and approved agents like bevacizumab. Success would differentiate the sponsor's offering in a market dominated by generic temozolomide and limited combination options.
Future Catalysts: Key milestones include Phase 2 efficacy and safety data readout, which would determine advancement to Phase 3. Regulatory feedback from major jurisdictions (FDA, EMA) on the combination approach will be critical. Patent composition-of-matter or method-of-use claims for the combination would enhance market exclusivity.
Expected Milestones: Phase 2 data presentation at oncology conferences, potential regulatory pre-submission meetings, Phase 3 initiation decision, and regulatory filings in major markets remain on the horizon. Timeline for these milestones is not yet disclosed.
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Intelligence compiled from public regulatory and clinical sources (FDA, EMA, ClinicalTrials.gov and company disclosures). Figures may be editorial or analyst estimates; verify against primary sources before relying on them.