Periodic Reporting for period 2 - I-CREATE (Fighting cancer with next generation oncolytic immunotherapy in ovarian, head & neck, and lung cancers (Immune Checkpoint Response Enabling Adenovirus Technology ))
Periodo di rendicontazione: 2023-04-01 al 2023-12-31
Cancer remains a major public health concern in Europe, with almost 2 million people dying of cancer each year. Cancer immunotherapy, including immune checkpoint inhibitors (ICI), have achieved clinical success in some patients, but insufficient presence of tumor neoepitopes, lack of tumor-specific T cells in the tumor and an immunosuppressive tumor microenvironment prevents long-term response in approximately 70-90% of patients. TILT Biotherapeutics is a clinical-stage biotechnology company developing novel gene therapies for cancer, based on its proprietary oncolytic viruses (OVs) armed with immunostimulatory molecules, which aim to immunologically heat up cold tumors. The company's lead asset, TILT-123, is an oncolytic adenovirus armed with two human cytokines, TNF alpha and IL-2, which has been tailored to provide the tumor with presence of immune cells, a prerequisite for ICIs to work and provide benefit for patients. Over 50 cancer patients have already been enrolled worldwide in TILT’s clinical studies involving the drug candidate. The treatments have been well tolerated and signs of efficacy have been seen in some of the patients, supporting further clinical development of TILT-123 and intravenous oncolytic immunotherapy.
The objective of this project was to assess safety, pharmacokinetics, clinical activity of TILT-123 as monotherapy and in combination with ICI, to determine the optimal dosing and to prepare for Phase 2. Overall, the project aimed to contribute to tackling the identified problems and needs of patients with advanced ovarian cancer, who face a significant burden on their health, families, communities, and healthcare systems.
The objective of this project was to assess safety, pharmacokinetics, clinical activity of TILT-123 as monotherapy and in combination with ICI, to determine the optimal dosing and to prepare for Phase 2. Overall, the project aimed to contribute to tackling the identified problems and needs of patients with advanced ovarian cancer, who face a significant burden on their health, families, communities, and healthcare systems.
WP1 - Phase 1b clinical trials in solid tumors
Over 50 patients were treated in TILT sponsored clinical studies in Europe and the U.S with TILT-123. A total of five Phase 1/1b clinical studies have been approved in Europe and/or the U.S. of which three Phase 1 studies were completed during this project for the initial dose escalation part of the study.
WP2 - Regulatory interactions and key-opinion leader relations
The team organized several regulatory workshops with the European and U.S. regulatory experts to work on the regulatory strategy towards Phase 2. Clinical and regulatory priorities were discussed and based on the thorough review of Phase 1 results, it was decided to continue with an additional Phase 1b study in ovarian cancer. The subsequent Phase 1b study is ready to start enrolling patients.
WP3 - Grant management, marketing and IPR
During the project, a communication plan was established, and business development activities were carried out and pharma companies met. The team also attended several congresses with the objective of presenting scientific results and business development for meeting pharma companies. For IPR, interactions with the national patent offices with respect to our patent application protecting the combination of TILT-123 and checkpoint inhibitors (WO/2020/249873) have been continued. Prosecution of TILT’s first patent family (WO/2014/170389) continued also.
WP4 - Chemistry, Manufacturing and Controls (CMC)
Manufacturing activities are ongoing with TILT's subcontractors responsible for manufacturing of TILT-123 for Phase 1/2 clinical studies. The supply of clinical material has been assured for all the ongoing clinical studies and inventory of the drug product is available for the upcoming clinical activities.
WP5 - Ethics
Before the initiation of each clinical study, there has been an external ethics assessment of the clinical documentation with the local authorities.
Over 50 patients were treated in TILT sponsored clinical studies in Europe and the U.S with TILT-123. A total of five Phase 1/1b clinical studies have been approved in Europe and/or the U.S. of which three Phase 1 studies were completed during this project for the initial dose escalation part of the study.
WP2 - Regulatory interactions and key-opinion leader relations
The team organized several regulatory workshops with the European and U.S. regulatory experts to work on the regulatory strategy towards Phase 2. Clinical and regulatory priorities were discussed and based on the thorough review of Phase 1 results, it was decided to continue with an additional Phase 1b study in ovarian cancer. The subsequent Phase 1b study is ready to start enrolling patients.
WP3 - Grant management, marketing and IPR
During the project, a communication plan was established, and business development activities were carried out and pharma companies met. The team also attended several congresses with the objective of presenting scientific results and business development for meeting pharma companies. For IPR, interactions with the national patent offices with respect to our patent application protecting the combination of TILT-123 and checkpoint inhibitors (WO/2020/249873) have been continued. Prosecution of TILT’s first patent family (WO/2014/170389) continued also.
WP4 - Chemistry, Manufacturing and Controls (CMC)
Manufacturing activities are ongoing with TILT's subcontractors responsible for manufacturing of TILT-123 for Phase 1/2 clinical studies. The supply of clinical material has been assured for all the ongoing clinical studies and inventory of the drug product is available for the upcoming clinical activities.
WP5 - Ethics
Before the initiation of each clinical study, there has been an external ethics assessment of the clinical documentation with the local authorities.
Three Phase 1 dose escalation studies were completed for the initial part of the study. These studies include the TILT-123 monotherapy study in all solid tumors (TUNIMO-NCT04695327), TILT-123 and TIL (tumor infiltration lymphocyte therapy) combination study in melanoma (TUNINTIL-NCT04217473), and one TILT-123 and ICI combination study.
The results of the TUNIMO trial were published at SITC in November 2023. TUNIMO was a single-arm open-label phase 1 clinical trial designed to assess the safety of TILT-123 monotherapy in patients with advanced solid tumors which are refractory to standard therapy. 20 patients were enrolled, and the most prevalent cancer types were sarcomas (35%), melanoma (15%) and ovarian cancer (10%). The results demonstrated a remarkable safety profile of TILT-123 monotherapy and showcased promising efficacy results, including anti-tumor activity and the induction of immune responses across different cancer types in patients who had exhausted traditional treatment options. TILT-123 was shown to achieve anti-tumor responses as a monotherapy, which can be seen in injected and non-injected lesions.
The results of the TUNINTIL trial were published at ESMO Immuno-Oncology end of 2023. The data announcement at ESMO-IO relates to 16 patients with checkpoint inhibitor (CPI) resistant progressive metastatic melanoma, who were treated with multiple intravenous and intratumoral injections of TILT-123 and a one- or two- time treatment with TILs. Responders include one with an ongoing partial response, one with a durable complete response, and two with long term (over ten months) stable disease.
Lastly, results of an additional Phase 1a study have been analyzed and will be published in Q2 2024.
The results of the TUNIMO trial were published at SITC in November 2023. TUNIMO was a single-arm open-label phase 1 clinical trial designed to assess the safety of TILT-123 monotherapy in patients with advanced solid tumors which are refractory to standard therapy. 20 patients were enrolled, and the most prevalent cancer types were sarcomas (35%), melanoma (15%) and ovarian cancer (10%). The results demonstrated a remarkable safety profile of TILT-123 monotherapy and showcased promising efficacy results, including anti-tumor activity and the induction of immune responses across different cancer types in patients who had exhausted traditional treatment options. TILT-123 was shown to achieve anti-tumor responses as a monotherapy, which can be seen in injected and non-injected lesions.
The results of the TUNINTIL trial were published at ESMO Immuno-Oncology end of 2023. The data announcement at ESMO-IO relates to 16 patients with checkpoint inhibitor (CPI) resistant progressive metastatic melanoma, who were treated with multiple intravenous and intratumoral injections of TILT-123 and a one- or two- time treatment with TILs. Responders include one with an ongoing partial response, one with a durable complete response, and two with long term (over ten months) stable disease.
Lastly, results of an additional Phase 1a study have been analyzed and will be published in Q2 2024.