Nyrada (ASX:NYR) has reported that its lead drug candidate Xolatryp demonstrated clear anti-tumour activity in a rodent model of liver cancer, both alone and in combination with the anthracycline chemotherapy doxorubicin.
Using a Huh7 cell line-derived xenograft model, tumours were allowed to reach 50-75 mm3 before treatment, and tumour volumes were tracked every other day for 2 weeks.
The combination of Nyrada's Xolatryp with doxorubicin produced the largest effect, showing a 57 per cent reduction in tumour volume versus vehicle at Day 14, compared with 41 per cent for doxorubicin alone and 32 per cent for Xolatryp as a monotherapy. Nyrada said that the combination results represent an approximately 39 per cent improvement in anti-tumour activity relative to doxorubicin alone, consistent with an additive effect.
Statistical analyses showed the combination produced significant tumour growth reduction as early as Day 4 and maintained that reduction through the study endpoint.
Doxorubicin alone achieved a significant reduction from Day 6, and Xolatryp alone from Day 10. Body weight changes were broadly consistent with expectations for the model, and safety monitoring included plasma cardiac troponin I measurements to assess heart health.
Nyrada observed a favourable trend in troponin I levels in animals receiving Xolatryp alone or in combination with doxorubicin, compared with doxorubicin alone. Two animals in the combination group died prematurely, an outcome the company attributed to tumour lysis syndrome, which can occur with highly active anti-cancer therapies and is manageable clinically.
Nyrada said it has lodged a provisional patent application for Xolatryp as an anti-cancer agent, complementary to an earlier allowed composition-of-matter patent application, and that the data support further preclinical evaluation across additional tumour types where anthracyclines remain the standard of care.
The company also plans additional preclinical cardiomyopathy studies to assess Xolatryp’s potential to mitigate doxorubicin-associated cardiac injury and to explore clinically translatable systemic dosing strategies.
Nyrada Managing Director and CEO James Bonnar said, “This study demonstrates highly encouraging proof-of-concept of a clear additive benefit over a standard-of-care treatment, consistent with enhanced anti-tumour activity of doxorubicin when combined with Xolatryp.” He added, “The results support the potential of Xolatryp to improve therapeutic outcomes in cancer patients treated with anthracycline drugs.”