Periodic Reporting for period 1 - TUMAGNOSTIC (A disruptive hypoxia activated prodrug for the treatment of resistant cancers: an AI-driven approach)
Reporting period: 2024-01-01 to 2024-12-31
Convert Pharmaceuticals SA (Convert) is a drug development company dedicated atleveraging tumour hypoxia for therapeutic advantage. Its leading candidate, CP-506, is a hypoxia-activated prodrug (HAP) that becomes active within tumours, exhibiting low toxicity. In addition to drug development, Convert specializes in biomarker innovation for precision medicine. The company is conducting a Phase I-IIa clinical trial for CP-506 (TUMAGNOSTIC) and holds intellectual property (IP) for another HAP that has been tested in Phase I and II trials.
The primary goal of TUMAGNOSTIC is to carry out an early-stage (Phase I and IIa), first-in-human clinical trial of CP-506. The trial is designed as an open-label, uncontrolled, multicenter, multiple-dose study. It has already been approved by regulatory authorities in the Netherlands and Belgium (CTD). The trial's main objective is to evaluate safety and tolerability of CP-506, both as a standalone treatment and in combination with other therapies, such as immune checkpoint inhibibors or carboplatin. Secondary objectives include characterizing the pharmacodynamics and pharmacokinetics of CP-506 and determining its preliminary efficacy.
The trial will be conducted in three modules, each consisting of two parts: (A) accelerated dose escalation and (B) an expansion cohort. The project aims to advance CP-506 from Technology Readiness Level (TRL) 5 to TRL 6 by completing Phase I clinical trials and laying the groundwork for TRL 7, which corresponds to the completion of Phase II clinical trials.
Convert employs an innovative tumour-agnostic strategy for this project, integrating AI-driven biomarkers to identify patients most likely to respond positively. This approach seeks to maximize treatment efficacy and minimize side effects, addressing challenges associated with previous HAPs.
A robust business development strategy will ensure that the project’s outcomes are effectively translated into further commercial development.
The primary goal of TUMAGNOSTIC is to carry out an early-stage (Phase I and IIa), first-in-human clinical trial of CP-506. The trial is designed as an open-label, uncontrolled, multicenter, multiple-dose study. It has already been approved by regulatory authorities in the Netherlands and Belgium (CTD). The trial's main objective is to evaluate safety and tolerability of CP-506, both as a standalone treatment and in combination with other therapies, such as immune checkpoint inhibibors or carboplatin. Secondary objectives include characterizing the pharmacodynamics and pharmacokinetics of CP-506 and determining its preliminary efficacy.
The trial will be conducted in three modules, each consisting of two parts: (A) accelerated dose escalation and (B) an expansion cohort. The project aims to advance CP-506 from Technology Readiness Level (TRL) 5 to TRL 6 by completing Phase I clinical trials and laying the groundwork for TRL 7, which corresponds to the completion of Phase II clinical trials.
Convert employs an innovative tumour-agnostic strategy for this project, integrating AI-driven biomarkers to identify patients most likely to respond positively. This approach seeks to maximize treatment efficacy and minimize side effects, addressing challenges associated with previous HAPs.
A robust business development strategy will ensure that the project’s outcomes are effectively translated into further commercial development.
Clinical Progress: The project has made significant strides in its clinical phase. The electronic Case Report Form (eCRF) has been finalized and successfully launched, marking a crucial milestone in data collection and management. One clinical center has officially initiated the study, setting the stage for patient recruitment and data gathering. A notable achievement is the inclusion of the first patient in the Phase I clinical trial. This patient has shown no toxicity and demonstrated a favorable pharmacokinetic (PK) profile, which is encouraging for the drug's safety and efficacy. Additionally, the clinical trial has been successfully transferred to the new CTR.
Manufacturing and Production: Progress has been made in the drug manufacturing process. A new batch of drug substance has been manufactured. Furthermore, the project has contractualised for the manufacturing of a new batch of drug product, which will be crucial for subsequent clinical phases.
Imaging and Analysis: The project team has developed a Standard Operating Procedure for imaging analysis, which will ensure consistency and reliability in interpreting imaging data. A phantom study has also been conducted on the imaging equipment, in order to have validated analysis methods.
Intellectual Property and Pipeline Development: Significant efforts have been made to expand and strengthen the project's IP portfolio. The team has analysed other drug candidates for Convert's pipeline, broadening the potential for future developments. Notably, Convert has acquired the IPR over another HAP, which is a valuable addition to the drug portfolio, as it further diversifies the pipeline.
Industry Partnerships: The project team has been proactive in establishing connections within the pharmaceutical industry. Ongoing contacts with potential partners in the pharma industry are being maintained, which could lead to valuable collaborations, funding opportunities, or eventual commercialization pathways.
Manufacturing and Production: Progress has been made in the drug manufacturing process. A new batch of drug substance has been manufactured. Furthermore, the project has contractualised for the manufacturing of a new batch of drug product, which will be crucial for subsequent clinical phases.
Imaging and Analysis: The project team has developed a Standard Operating Procedure for imaging analysis, which will ensure consistency and reliability in interpreting imaging data. A phantom study has also been conducted on the imaging equipment, in order to have validated analysis methods.
Intellectual Property and Pipeline Development: Significant efforts have been made to expand and strengthen the project's IP portfolio. The team has analysed other drug candidates for Convert's pipeline, broadening the potential for future developments. Notably, Convert has acquired the IPR over another HAP, which is a valuable addition to the drug portfolio, as it further diversifies the pipeline.
Industry Partnerships: The project team has been proactive in establishing connections within the pharmaceutical industry. Ongoing contacts with potential partners in the pharma industry are being maintained, which could lead to valuable collaborations, funding opportunities, or eventual commercialization pathways.
The project has delivered promising initial findings that advance the current state of the art in precision medicine and cancer treatment:
- A patient has been successfully enrolled in the clinical trial, demonstrating no toxicity. Favorable pharmacokinetic profile of CP-506 has been obtained, with minimal presence of CP-506M metabolite, indicating intratumoural activation of the prodrug with minimal leakage. The PK analysis from the first patient shows a prolonged half-life. The initial PK analysis for Patient #1 also indicates a favourable exposure is achieved. Anticipating PK is linear with dose (as observed preclinically), then therapeutically relevant exposures, based on PK/PD across multiple tumour xenograft models, will be achieved by Cohort 2 and above. The results are also in line with the absence of AKR1C3 off-target activation.
- The project monitors patients based on biomarkers linked to tumour hypoxia and homologous recombination defects. This strategy is designed to identify patients most likely to benefit from the treatment, potentially enhancing efficacy while minimizing unnecessary treatments.
To ensure the continued success and broader adoption of this innovative therapy, several critical areas require focus:
- Scaling up the Phase I-IIa study is essential to further evaluate the safety of CP-506, both as a monotherapy and in combination with standard-of-care treatments.
- Enrolling more patients will provide robust and comprehensive data on the drug's safety and efficacy, supporting its clinical development.
- Additional funding is required to sustain ongoing research and clinical trials. Convert is actively raising a Series A funding round to secure the necessary resources to advance the project.
- A patient has been successfully enrolled in the clinical trial, demonstrating no toxicity. Favorable pharmacokinetic profile of CP-506 has been obtained, with minimal presence of CP-506M metabolite, indicating intratumoural activation of the prodrug with minimal leakage. The PK analysis from the first patient shows a prolonged half-life. The initial PK analysis for Patient #1 also indicates a favourable exposure is achieved. Anticipating PK is linear with dose (as observed preclinically), then therapeutically relevant exposures, based on PK/PD across multiple tumour xenograft models, will be achieved by Cohort 2 and above. The results are also in line with the absence of AKR1C3 off-target activation.
- The project monitors patients based on biomarkers linked to tumour hypoxia and homologous recombination defects. This strategy is designed to identify patients most likely to benefit from the treatment, potentially enhancing efficacy while minimizing unnecessary treatments.
To ensure the continued success and broader adoption of this innovative therapy, several critical areas require focus:
- Scaling up the Phase I-IIa study is essential to further evaluate the safety of CP-506, both as a monotherapy and in combination with standard-of-care treatments.
- Enrolling more patients will provide robust and comprehensive data on the drug's safety and efficacy, supporting its clinical development.
- Additional funding is required to sustain ongoing research and clinical trials. Convert is actively raising a Series A funding round to secure the necessary resources to advance the project.