Periodic Reporting for period 1 - NEOpTTL (Innovative approach to an Individualised T-Cell Immunotherapy for cancer, using Personalised Tumour Trained Lymphocytes (pTTL) that is reliable, cost-effective, scalable and easy to implement)
Reporting period: 2023-11-01 to 2024-10-31
Adoptive T cell therapy utilizing high-precision neoantigen targeting is a promising concept for the treatment of solid tumors. NEOGAP has developed a personalised adoptive T cell therapy for treating solid tumours based on two proprietary technologies: PIOR® machine learning software and EpiTCer®. PIOR® is used to identify tumour-specific mutations that give rise to neoantigens, i.e. proteins exclusively expressed in the tumour, and to select and design neoantigens that can be targeted by T cells. EpiTCer® enables efficient delivery of neoantigens and activation of neoantigen specific T cells. Our cancer immunotherapy consists of personalised Tumour Trained Lymphocytes (pTTL), which are autologous T-cells harvested from regional lymph nodes (RLN). During the pTTL production process, neoantigen-driven T-cell expansion of RLN cells is obtained in the context of EpiTCer, generating a T cell product harbouring highly tumour-reactive T-cell clones. pTTL is re-infused to the patient where they infiltrate tumours and kill cancer cells, leaving healthy cells untouched. The therapy is broadly applicable to many cancer types, including solid tumours where current cancer immunotherapy is less effective due to lack of immune cellinfiltration to the tumour. Thus pTTL can potentially be applied in cancers with a high unmet medical need. A phase I/IIa First in Human (FIH) clinical trial of pTTL in advanced, Stage IV, colorectal cancer (CRC) patients is ongoing. The primary objective of the trial is to show safety and tolerability of pTTL. Secondary, efficacy parameters like objective response, overall survival, and progression-free survival will be assessed and biomarkers will be explored for signs of afficacy.
In this EIC accelerator project, NEOpTTL, we plan to complete the phase I/IIa clinical trial of the therapy, to optimise the pTTL manufacturing process for the next clinical trials and to establish a development strategy to marketing approval of pTTL.
In this EIC accelerator project, NEOpTTL, we plan to complete the phase I/IIa clinical trial of the therapy, to optimise the pTTL manufacturing process for the next clinical trials and to establish a development strategy to marketing approval of pTTL.
The phase I/IIa clinical trial of pTTL in advanced colorectal cancer patients is ongoing and preparations for manufacturing scale out and for the next clinical development stage have been performed according to the project plan .
Main achievements: during the first reporting period (RP1) of NEOpTTL:
• The project has successfully been started.
• Nineteen patients have been included in the clinical trial. One patient has been treated with pTTL.
• The clinical trial protocol has been developed to mitigate trial delays and to ensure that the trial can be finalised.
• A cryopreservation protocol for the pTTL product has been implemented.
• A contract has been signed with the CDMO NorthX and a study plan for pTTL manufacturing agreed on.
• A regulatory strategy plan for the next clinical trial is in place.
• European Medicines Agency (EMA) has granted pTTL a classification as an Advanced Therapy Medicinal Product (ATMP) under Regulation (EC) No. 1394/2007 on advanced therapy medicinal products.
Main achievements: during the first reporting period (RP1) of NEOpTTL:
• The project has successfully been started.
• Nineteen patients have been included in the clinical trial. One patient has been treated with pTTL.
• The clinical trial protocol has been developed to mitigate trial delays and to ensure that the trial can be finalised.
• A cryopreservation protocol for the pTTL product has been implemented.
• A contract has been signed with the CDMO NorthX and a study plan for pTTL manufacturing agreed on.
• A regulatory strategy plan for the next clinical trial is in place.
• European Medicines Agency (EMA) has granted pTTL a classification as an Advanced Therapy Medicinal Product (ATMP) under Regulation (EC) No. 1394/2007 on advanced therapy medicinal products.
pTTL is a novel innovative personalised cancer therapy with curative potential, based on unique machine-learning/AI and immune stimulation technologies. The initiation of a FIH trial marks an important milestone towards the establishment of pTTL, with a high curative potential for a large number of patients. The goal is to achieve market authorisation approval for pTTL. Preparations are ongoing to reach this goal, including optimisation of the pTTL production process aiming at large scale manufacturing, drafting a clinical development strategy and setting the regulatory roadmap to market. The results of the ongoing FIH Phase I/IIa trial will lay the ground for the next clinical trial, a Phase II trial that will enable registration and market authorisation of pTTL. Work has already been initiated to identify patient population(s) with the highest unmet medical need and potential highest clinical benefit and to find suitable clinical sites across EU and EAA for the Phase II trial. As soon as positive results are emerging from the FIH trial, actions will also be taken to approach markets for commercialisation.