Congrats to ARQL and especially CLL (a type of blood cancer) patients on the impressive early-stage data presented today at a poster session at the European Haematology Association annual conference, on ARQL's experimental reversible Btk kinase inhibitor, ARQL 531, for patients who relapse on IBRUVICA (Ibrutinib) treatment (ARQL 531 poster at EHA '19). The majority of patients who relapse on ibrutinib acquire a particular mutation in their Btk kinase (Woyach et al. 2017). This mutation is the target of ARQL 531. In the data presented at EHA today, for patients who progressed on 2 or more prior therapies including a covalent Btk inhibitor such as Ibrutinib, and who had the target Btk mutation, 4 of 6 patients had their tumors shrink by more than 50% in the highest evaluable dose (See right graph in figure below). Further noteworthy was the partial response in a patient with Richter's transformation (RT), a particularly deadly transformation that occurs in some CLL patients on therapy, with median survival of less than 4 months for patients whose cancers transforms to RT after ibrutinib therapy (Woyach et al. 2017). There is an urgent need for effective therapies for RT (Khan et al.).
ARQL 531 shows the exciting promise of multiple levels of targeted cancer therapies where as we learn how cancers overcome an initial targeted therapy, we strike with a second therapy that targets this resistance mechanism. Signs of efficacy appeared for this very promising next generation Btk kinase inhibitor at the ASH conference in December 2018 as dose escalation was reaching meaningful dose levels and a low-level initial efficacy signal was becoming clear. First reports of an official partial response were reported on an investor call in March, in the first patient with the target Btk mutation when treated with effective levels of ARQL 531. However, today's data, showing over 50% tumor shrinkage in 4 of 6 evaluable CLL patients at the 65 mg dose, and no increase in disease in any of the patients, demonstrates a clear proof of concept for this drug (See right graph below).
Figure from ARQL poster at EHA '19
Congratuatlons to ARQL and especially CLL patients, who now have another hopeful therapeutic targeted therapy in the clinic. Patients who have CLL and have progressed on a prior Btk inhibitor such as IBRUVICA should assure their physicians are paying close attention to the expanding set of clinical trials for ARQL 531 that are likely to commence in months. For those of us that have invested in ARQL this has been a very exciting run with ARQL now up over 300% this year. We were fortunate with some bullish Call and Put spread stock options plays this week with the call play returning 150% if ARQL stays above $7.50. Biopharma investing is very tricky with most drugs failing in clinical trials and investors in this space having to withstand numerous failures for every victory. ARQL 531 is a great example of how sometimes, exciting science can play out into exciting returns for investors.