With the recent publication of the topline results from the monotherapy FIDES-01 study for Basilea's lead oncology candidate derazantinib in biliary cancer (iCCA), details from the dose ranging FIDES-02 study have been presented recently at ASCO GU.
FIDES-02 (as well as FIDES-03) is an extremely important study and will likely help establish the competitive positioning of derazantinib in the increasingly competitive FGFR inhibitor class. Of the approved FGFR inhibitors, Basilea appears to have the sole ability to help reverse the immunosuppressive state found in many cancers thanks to its activity against the CSF-1/CSF1R axis. As a result, derazantinib may be able to augment the activity of the checkpoint inhibitor class in cancers where their activity has been found to be suboptimal to date. Additionally, we believe that this additional property could be beneficial with respect to the risk of resistance emerging against the FGFR inhibitor class in the longer term.
Basilea has designed the FIDES-02 study to recruit patients who are cisplatin-ineligible or who have failed on first-line therapy (or prior treatment with FGFR inhibitors). The trial comprises three open-label studies in urothelial cancer with an FGFR gene alteration to assess the activity of derazantinib alone or in combination with Tecentriq. One additional arm in the study established the recommended phase 2 dose of the combination of derazantinib and Tecentriq. The primary endpoint completion date is 2022.
We have previously noted the reassuring ability to combine derazantinib and Tecentriq at the approved Tecentriq and optimal derazantinib doses. The most commonly reported adverse events were fatigue/asthenia, nausea and diarrhoea. With respect to encouraging signs of efficacy, albeit in biliary cancer we note that one patient harbouring an FGFR2 gene fusion remains ongoing in the study for more than nine months who has benefited from combination treatment with a partial response with continued tumour shrinkage. Given that the combination of derazantinib and Tecentriq resulted in no unexpected and unmanageable toxicities, Basilea intends to further evaluate the potential of derazantinib by altering the ongoing FIDES-02 study protocol to evaluate a higher dose of derazantinib in two of the cohorts. The intention here is to explore whether increasing the derazantinib dose to the previously established maximum tolerated daily dose, (which is circa 30% higher than the 300mg dose used in FIDES-02), could deliver additional benefits in monotherapy as well as in combination.
While the topline results of FIDES-01 serve to derisk the clinical risk, it will be the results of FIDES-02 (urothelial cancer) and FIDES-03 (gastric cancer) which will likely determine the commercial potential for derazantinib. The combination with the checkpoint inhibitor class certainly holds significant promise and we look forward with keen anticipation as results emerge later this year and next.
We have calculated a discounted cash flow fair value of CHF 120 for Basilea.
IMPORTANT:
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.