Derazantinib, as an inhibitor of FGFR1-3, has already shown potent activity in the treatment of bile duct cancer in patients who harbour gene fusions as well as mutations and alterations.
Although bile duct and bladder cancers may represent highly competitive fields for derazantinib, following the approvals of Pemazyre, Balversa, and now Truseltiq, each of these FGFRs possess different attributes. Derazantinib's differentiation includes the inhibition of the CSF1R. CSF1R is a key component in maintaining the immunosuppressive microenvironment. Basilea is exploring this additional property by combining derazantinib with the checkpoint inhibitor atezolizumab (Roche's Tecentriq). Basilea believes there is potential to improve Tecentriq's activity in both urothelial (FIDES-02) and gastric cancer (FIDES-03).
While there is good evidence supporting the efficacy of FGFR inhibition in bile duct and urothelial cancer, prospects are more challenging in the gastric cancer setting. Nevertheless, we have previously highlighted the activity of Five Prime Therapeutics' FGFR2b targeted antibody bemarituzumab in gastric cancer, which was sufficiently encouraging to attract the attention of Amgen as it paid $1.9bn for Five Prime in March 2021.
Encouragingly for derazantinib, preclinical data presented today at the ACR-NCI-EORTC (ANE) virtual International Conference on Molecular Targets and Cancer Therapeutics, further support the role of derazantinib in gastric cancer and, in particular, its additional activity against CSF1R. Data presented at the conference suggested synergistic anti-tumour effects with paclitaxel, building on the previous preclinical data reported in monotherapy. The data presented were from several gastric cancer models, which included in-vivo tumour models representing different FGFR aberrations. Data in more prevalent FGFR gene fusion models reported complete regression. Importantly, where higher levels of immunosuppressive M2-tumor-associated macrophages were involved, the combination with paclitaxel and derazantinib generated a more profound response. Clearly, these data bode well for the forthcoming FIDES-03 data which are evaluating derazantinib in combination with paclitaxel (and Tecentriq) in gastric cancer. Positive results should help further inform the differentiated profile of derazantinib versus its FGFRi competitors.
We have calculated a discounted cash flow fair value of CHF120 for Basilea.
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Basilea Pharmaceutica is a client of Calvine Partners and as such, this publication is not independent and should be considered a marketing communication under FCA Rules. None of the information contained in this publication should be considered as any form of advice.