Periodic Reporting for period 1 - Histotype Px (Precision biomarker based on digital pathology and artificial intelligence to guide fast and cost-effective personalized treatment decision support for colorectal cancer patients)
Período documentado: 2024-06-01 hasta 2025-05-31
Colorectal cancer (CRC) is the third most common and the second most deadly cancer globally, with approximately 2 million new cases and 0.9 million deaths every year. Both numbers are expected to grow 30% by 2030, according to WHO estimates. The economic burden in Europe alone exceeds €19 Billion.
Like in other cancers, CRC severity is assessed from stage 0 (local tumour) to stage IV (metastasis to distant sites). Approx. 70% of new CRC cases are diagnosed at Stages II or later due to lack of symptoms (i.e. a “silent killer”). After diagnosis, surgical resection is the standard-of-care (SoC) for stage II or III patients, and ~1 million of these undergo surgery every year. During surgery, the resected tumour is sent to a pathology lab to determine the patient’s stage and histological risk profile, which in turn will help to determine the treatment plan. In SoC, surgery is followed by 3 to 6 months of adjuvant chemotherapy (ACT) to reduce the risk of recurrence and death.Most patients are cured after surgery, but due to the lack of proper risk stratification, most patients receive ACT to “do everything we can”. Therefore, the vast majority of patients are currently exposed to toxic ACT with no benefit. This treatment hospitalizes up to 50% of patients due to serious side effects and up to 1% die. After the treatment, 30% are left with chronic health issues from ACT, reducing quality of life. As such, ACT must be reserved to patients who are likely to benefit from it. This represents a large unmet medical need recognized by the European Society for Medical Oncology (ESMO) in its clinical practice guidelines, which state that there is a "clinical need for better biomarkers to improve risk stratification, patient selection and inform therapy decision making." DoMore Dx was founded to directly address this unmet medical need, starting with CRC prognosis and treatment and have developed a ground-breaking digital biomarker, Histotype Px® Colorectal (hereafter Histotype Px), that provides clinicians with a rapid (i.e. minutes), cost-effective and highly accurate biomarker (hazard ratio >10) to guide personalized treatment decisions in colorectal cancer, improving patients’ outcomes and avoiding unnecessary health care costs. The existing documented performance of Histotype Px is very solid, however it needs to be broadened with more clinical validations to become the gold standard test for all CRC patients (i.e. to be integrated into the clinical guidelines in EU and US) and to be eligible for reimbursement. Importantly, the amount of evidence needed to recommend a patient to forego ACT is much higher than when adopting or adding a new treatment. Since this is a major clinical decision for each patient, additional validation studies on historical trials in more geographies and treatment regimens are required to fully validate the prognostic and predictive value of Histotype Px. The key objectives of the current project is therefore to generate the required clinical evidence and to develop the Histotype Px platform to satisfy all clinical and regulatory requirements for market entry, adoption and reimbursement in target markets.
Like in other cancers, CRC severity is assessed from stage 0 (local tumour) to stage IV (metastasis to distant sites). Approx. 70% of new CRC cases are diagnosed at Stages II or later due to lack of symptoms (i.e. a “silent killer”). After diagnosis, surgical resection is the standard-of-care (SoC) for stage II or III patients, and ~1 million of these undergo surgery every year. During surgery, the resected tumour is sent to a pathology lab to determine the patient’s stage and histological risk profile, which in turn will help to determine the treatment plan. In SoC, surgery is followed by 3 to 6 months of adjuvant chemotherapy (ACT) to reduce the risk of recurrence and death.Most patients are cured after surgery, but due to the lack of proper risk stratification, most patients receive ACT to “do everything we can”. Therefore, the vast majority of patients are currently exposed to toxic ACT with no benefit. This treatment hospitalizes up to 50% of patients due to serious side effects and up to 1% die. After the treatment, 30% are left with chronic health issues from ACT, reducing quality of life. As such, ACT must be reserved to patients who are likely to benefit from it. This represents a large unmet medical need recognized by the European Society for Medical Oncology (ESMO) in its clinical practice guidelines, which state that there is a "clinical need for better biomarkers to improve risk stratification, patient selection and inform therapy decision making." DoMore Dx was founded to directly address this unmet medical need, starting with CRC prognosis and treatment and have developed a ground-breaking digital biomarker, Histotype Px® Colorectal (hereafter Histotype Px), that provides clinicians with a rapid (i.e. minutes), cost-effective and highly accurate biomarker (hazard ratio >10) to guide personalized treatment decisions in colorectal cancer, improving patients’ outcomes and avoiding unnecessary health care costs. The existing documented performance of Histotype Px is very solid, however it needs to be broadened with more clinical validations to become the gold standard test for all CRC patients (i.e. to be integrated into the clinical guidelines in EU and US) and to be eligible for reimbursement. Importantly, the amount of evidence needed to recommend a patient to forego ACT is much higher than when adopting or adding a new treatment. Since this is a major clinical decision for each patient, additional validation studies on historical trials in more geographies and treatment regimens are required to fully validate the prognostic and predictive value of Histotype Px. The key objectives of the current project is therefore to generate the required clinical evidence and to develop the Histotype Px platform to satisfy all clinical and regulatory requirements for market entry, adoption and reimbursement in target markets.
The Histotype Px project was designed around six work packages to achieve the key objectives. As of May 2025, the main achievements include completed data analysis, publication and submitted publications on expanded clinical validation of the biomarker in external hospital settings and patient samples in Europe, the US and Japan, both as a stand-alone biomarker and in combination with liquid biopsies (WP2). Importantly, clinical data show strong performance of the Histotype Px biomarker both in treated and non-treated patients, underscoring the potential predictive value of the test, which strengthens the overall evidence package to be submitted for guideline inclusion (WP6), with first submission to clinical guidelines expected in 2025. As part of WP 4, which will develop a scalable cybersecure, commercial cloud service that fulfills all regulatory requirements (WP5), stringent data security and privacy controls will be implemented to safeguard against unauthorized access, data breaches, and other potential threats. A cloud-based portal has been developed according to specified requirements, and a compliance software tool has been implemented.
The current project goes beyond the state of the art in several aspects. Histotype Px is the the world's first CE-marked AI-based digital biomarker to guide treatemt decisions in stage II and stage III colorectal cancer, and the first with extensive clinical validations on large patients samples across multiple external hospital settings in multiple territories. Histotype Px provides several unique advantages over existing solutions: 1) Speed: short turnaround time enabling ACT initiation within the optimal treatment window; 2) Accuracy: Directly predicts long-term survival, enabling robust patient stratification into low-, intermediate-, and high-risk groups; 3) Cost-effectiveness: Utilizes routine slides, eliminating the need for costly molecular testing; 4) Scalable distribution: Seamlessly integrates into existing pathology lab and clinical workflows, with no need for new hardware or procedures.