AXA has partnered with AZ to explore a combination of Bcl-2 inhibitors and BTK inhibitors.

The study, a global multi-center, open, Ib/II dose efficacy exploration study, was designed to assess the safety, tolerance, and initial evaluation of effectiveness of APG-2575 monodrug or combined Calquance treatment for recurrent chronic lymphocytic leukemia/small lymphocyte lymphoma (CLL/SLL)The pilot program is being launched in the United States, Europe and Australia, and the first patient administration has been completed in the United StatesCLL/SLL is a mature B lymphocyte clone proliferation tumor, is the highest incidence of adult leukemia in developed countries in Europe and the United States, accounting for about 30% of all leukemia, the annual incidence rate of 2-6/10 million people, the incidence of people over 65 years of age as high as 128/100,000 peopleAlthough the first-line solution significantly improves the initial treatment and remission rate of CLL/SLL patients, but the need for long-term medication to control the disease, once relapsed often the prognosis is very poorAPG-2575 is a new oral Bcl-2 selective inhibitor developed by AXA Pharmaceuticals to restore the procedural death mechanism of tumor cells (cell apoptosis) by selectively inhibiting Bcl-2 protein family members, thereby killing tumors and developing a variety of hematologic malignanciesAt present, in the United States, Australia, China has launched the drug single drug Phase I clinical trials, simultaneously promote the clinical development of multiple blood tumor indicationsAmong the bCL-2 products, AbbVie's venetoclax is currently approved for second-line treatment carrying 17p-removed relapse or refractive CLL, and the Venetoclax Joint Primary (CD20) first-line treatment CLL/SLL FDA has also been granted breakthrough therapy in March 2019BTK (Bruton tyrosine protein kinase) is an important signal molecule of B-cell receptor pathway, expressed at various stages of B-cell development, participated in regulating the proliferation, differentiation and apoptosis of B cells, plays an important role in the survival and diffusion of malignant B cells, and is currently a hot research topic for B-cell tumors and B-cell immune diseasesThe world's first BTK inhibitor ibtinib has been approved for treatment of CLL/SLL, including single-drug second-line/first-line treatment OfL/SLL, and joint CD20 mono-resistance first-line treatment for adult CLL/SLLBCL-2 and BTK are two hot targets of concern in recent years, and the exploration of BCL-2 inhibitors and BTK inhibitors for the combination of treatments for CLL/SLL has progressedIn particular, a 2019 study from the MD Anderson Cancer Center in the New England Journal of Medicine showed that 25 of the 26 assessable patients received CR/CRi during the 18-month period of Ibutini's joint venetoclax treatment, and the CR/CRi rate was 96 percent (95 percent CI, 80 percent 100 percent)In other words, almost all patients reached CR/CRi, and the association of the two did not significantly increase adverse reactionsAlthough compared with venetoclax, and although the assessment sample case is small, this record high rate of alarming response and depth of response is sufficient to motivate researchers to conduct larger clinical studies to further confirm that BTK inhibitors in combination with Bcl-2 inhibitors for PFS and OS in CLL/SLL patients, the treatment will most likely change the first-line treatment of CLLthe study is also the basis for a joint drug study between APG-2575 (BCL-2 inhibitors) and acalabrutinib (BTK inhibitors)Acalabrutinib is a second-generation BTK inhibitor with a higher specificity to BTK than ibtinib, and the combination of APG-2575-acalabrutinib is expected"We are pleased to have reached this clinical partnership with AstraZeneca's Acerta," said DrDajun Yang, Chairman and CEO of AxaPharmaceutical, APG-2575 is an important research variety of AXA pharmaceutical apoptosis product pipeline, which shows great potential in the treatment of malignant tumors in the blood system This partnership will accelerate clinical development of aPG-2575 worldwide Safe and effective combination drug use is an important trend in tumor treatment, and the potential of Bcl-2 inhibitors and BTK inhibitors cannot be ignored We look forward to the potential synergies between APG-2575 and Calquence to provide more treatment possibilities for CLL/SLL patients worldwide "
References 1 Jain N, Keating M, Thompson P, et al Ibrutinib and venetoclax for first-line treatmentofC CLL N Engl J Med 2019;380:2095-2103 Wiestner A Ibrutinib and venetoclax - doubling down on CLL N Engl J Med2019; 380:2169-2171.