Periodic Reporting for period 2 - CURE-PDAC (Acceleration of the world’s first autotaxin inhibitor for the treatment of pancreatic cancer (PDAC))
Reporting period: 2024-01-01 to 2025-03-31
Pancreatic cancer is one of the most aggressive and lethal cancers, with a 5-year survival rate of only 13%. Currently, treatments for pancreatic cancer are largely ineffective, potentially due to the high degree of stromal fibrotic scar tissue in the tumour. This fibrotic scar tissue acts as a physical barrier to limit the penetration of chemo- and immune therapies, is responsible for secreting factors that dampen the immune response, and provides an intrinsic cancer support mechanism. There is a high unmet medical need for novel pancreatic cancer therapies, and targeting the fibrotic scar tissue is a promising novel strategy.
Cambritaxestat (IOA-289) is such novel therapy, an inhibitor of autotaxin, an enzyme that is key in driving the fibrotic scar tissue and therefore pancreatic tumour growth. IOA-289 is an oral therapy that can be taken at home, adding to patient convenience and compliance. IOA-289 promises to be a safe and tolerable drug which could be used alone, or in combination with existing treatments to delay progression of pancreatic cancer and beyond.
The CURE-PDAC project assessed the safety and tolerability of IOA-289 in a clinical trial with pancreatic cancer patients in combination with standard chemotherapy. Early efficacy parameters and novel biomarkers were explored. The results of the CURE-PDAC project are accelerating the development of IOA-289 to be established as a novel therapy bringing substantial benefit to cancer patients.
Cambritaxestat (IOA-289) is such novel therapy, an inhibitor of autotaxin, an enzyme that is key in driving the fibrotic scar tissue and therefore pancreatic tumour growth. IOA-289 is an oral therapy that can be taken at home, adding to patient convenience and compliance. IOA-289 promises to be a safe and tolerable drug which could be used alone, or in combination with existing treatments to delay progression of pancreatic cancer and beyond.
The CURE-PDAC project assessed the safety and tolerability of IOA-289 in a clinical trial with pancreatic cancer patients in combination with standard chemotherapy. Early efficacy parameters and novel biomarkers were explored. The results of the CURE-PDAC project are accelerating the development of IOA-289 to be established as a novel therapy bringing substantial benefit to cancer patients.
The CURE-PDAC project was started with the timely submission of all required clinical trial documentation to the involved regulatory agencies and ethical committees. The IOA-289 study drug substance was manufactured and oral drug product capsules were produced. After the regulatory approval in Italy, the Phase 1b clinical study was started and the first patient was dosed with IOA-289 in November 2022. A total of 16 patients across four increasing dose level cohorts have been dosed in the clinical trial. The dose escalation was completed in February 2025 with the independent Safety Monitoring Committee concluding that dose levels of 100 to 800 mgIOA-289, twice daily, were safe and tolerable.
In parallel to the clinical activities, an Orphan Drug Designation request had been submitted and was awarded by the FDA in March 2024. An International Nonproprietary Name (INN) has been requested at the WHO and the proposed INN cambritaxestat was received. Two symposia with key experts in the field were held and provided valuable input to the project’s development.
Early 2024, iOnctura secured a EUR 80 million series B financing led by new investor Syncona Limited with participation by the EIC Fund, the venture arm of the European Innovation Council (EIC), as well as existing investors M Ventures, Inkef Capital, VI Partners, Schroders Capital and 3B Future Health Fund. The financing supports acceleration of the development of multiple clinical stage programs, including cambritaxestat in pancreatic cancer and beyond.
In parallel to the clinical activities, an Orphan Drug Designation request had been submitted and was awarded by the FDA in March 2024. An International Nonproprietary Name (INN) has been requested at the WHO and the proposed INN cambritaxestat was received. Two symposia with key experts in the field were held and provided valuable input to the project’s development.
Early 2024, iOnctura secured a EUR 80 million series B financing led by new investor Syncona Limited with participation by the EIC Fund, the venture arm of the European Innovation Council (EIC), as well as existing investors M Ventures, Inkef Capital, VI Partners, Schroders Capital and 3B Future Health Fund. The financing supports acceleration of the development of multiple clinical stage programs, including cambritaxestat in pancreatic cancer and beyond.
In the Phase 1b clinical study, IOA-289 was well tolerated in combination with standard chemotherapy across all tested dose levels. Patients in the higher-dose cohorts exhibited consistent reductions in pharmacodynamic marker LPA 18:2 and tumour marker CA19-9, and early evidence of clinical activity. The delayed but durable nature of observed responses supports a potential contribution of IOA-289’s immunomodulatory and anti-fibrotic mechanisms to the therapeutic effect of the chemotherapy. On the other hand, some biomarkers suggest that the chemotherapy counteracts part of IOA-289 activity. These initial results from the clinical study look promising and warrant further investigation and continuation of the project in pancreatic cancer and beyond.
We have made significant steps to show the biologic activity of IOA-289 in patients and highlight the importance of biomarker integration in early-phase oncology trials. However, further validation in larger cohorts and additional mechanistic studies are warranted to better characterize the therapeutic potential and predictive biomarkers for IOA-289 in cancer. A clinical study to explore the therapeutic action of IOA-289 as single agent in liver cancer is currently in planning. Based on the potential interference of the chemotherapy on IOA-289 activity, further research is also needed to identify the best combination treatments.
During the CURE-PDAC project, multiple scientific poster presentations and papers on the role of autotaxin in cancer were published. Based on this preclinical data, novel intellectual property has been filed on the use of IOA-289 in gastrointestinal tumours other than pancreatic cancer. In addition, a patent application has been submitted describing the chemistry, polymorphic form and formulation of IOA-289. A patent application on the synergistic use of the TGFβR1 (ALK5) inhibitor IOA-359 plus IOA-289 in liver cancer is in preparation.
We have made significant steps to show the biologic activity of IOA-289 in patients and highlight the importance of biomarker integration in early-phase oncology trials. However, further validation in larger cohorts and additional mechanistic studies are warranted to better characterize the therapeutic potential and predictive biomarkers for IOA-289 in cancer. A clinical study to explore the therapeutic action of IOA-289 as single agent in liver cancer is currently in planning. Based on the potential interference of the chemotherapy on IOA-289 activity, further research is also needed to identify the best combination treatments.
During the CURE-PDAC project, multiple scientific poster presentations and papers on the role of autotaxin in cancer were published. Based on this preclinical data, novel intellectual property has been filed on the use of IOA-289 in gastrointestinal tumours other than pancreatic cancer. In addition, a patent application has been submitted describing the chemistry, polymorphic form and formulation of IOA-289. A patent application on the synergistic use of the TGFβR1 (ALK5) inhibitor IOA-359 plus IOA-289 in liver cancer is in preparation.