Through deepening its layout in the hematoma field, Yasheng Pharmaceutical is gradually building a competitive barrier in this field. Meanwhile, the development of cell apoptosis pipeline varieties represented by the Bcl-2 inhibitor APG-2575 fully demonstrated the strong innovative research and development capabilities of Yasheng Pharmaceutical-B (06855).

On October 13, Yasheng Pharmaceutical announced that the registered phase III study of APG-2575 to treat initial CLL/SLL has successfully obtained clinical trial approval from the CDE of the Drug Evaluation Center of the State Drug Administration. This is another major milestone after the variety was approved by the US FDA in August this year to conduct a globally registered phase III clinical study to treat patients with treated CLL/SLL.

It is worth mentioning that the secondary market fully affirms the intrinsic value of Yasheng Pharmaceutical in the field of APG-2575 product development. Although the biomedical sector of the Hong Kong stock market has continued to fluctuate recently, Yasheng Pharmaceutical's stock price is still going against the market and achieving “six consecutive positive results,” with a cumulative increase of 14.54% over the past six trading days.

In fact, in recent years, in addition to receiving full endorsement from domestic and foreign authorities, Yasheng Pharmaceutical's innovative research has also received unanimous recognition from the global industry at various authoritative international conferences. Solid and steady innovative research and development has also brought Yasheng more opportunities for cooperative research and development with global multinational pharmaceutical companies.

According to the Zhitong Finance App, after obtaining clinical trial approval from the CDE, Yasheng Pharmaceutical issued an announcement on October 16, formally confirming the clinical cooperation agreement between the company and AstraZeneca. The two sides will jointly promote a registered phase III clinical study of APG-2575 combined with AstraZeneca's BTK inhibitor, cocoside (generic name: acotinib), for first-line treatment of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

The study is a global, multi-center, randomized, open, and key confirmatory phase III clinical study to evaluate the efficacy and safety of APG-2575 combined with acotinib compared with immuno-chemotherapy in patients with newly treated CLL/SLL.

This is a further clinical collaboration between Yasheng Pharmaceutical and AstraZeneca on the combined use of APG-2575 and acotinib. In June 2020, the company reached a clinical research partnership with Acerta Pharmaceuticals, a center of excellence in blood research and development at a global level, to conduct a global phase II clinical study on the combined treatment of the BCL-2 selective inhibitor APG-2575 being developed by Yasheng Pharmaceutical and Acerta Pharmaceuticals' BTK inhibitor, acotinib, to evaluate its safety, tolerability, and efficacy in CLL/SLL patients.

The clinical study showed the strong potential for combined treatment of APG-2575 with acotinib. The data showed that the objective response rate (ORR) of this combination therapy in patients with relapsed/refractory (R/R) CLL/SLL reached 98%, ORR reached 100% in patients with initially treated CLL/SLL, and still maintained a good level of safety comparable to monotherapy. The results of the study were presented as an oral report at the 2022 American Society of Hematology (ASH) Annual Meeting.

Judging from the indication market, CLL/SLL is a mature B-lymphocyte clonal proliferative tumor. It mostly occurs in elderly patients. It is one of the most common types of adult leukemia. It accounts for a quarter of leukemia cases in Western countries, and there are more than 100,000 new cases worldwide every year.

In China, the incidence of CLL/SLL is clearly on the rise, and is characterized by a low age of onset and high degree of aggressiveness, which seriously threatens the lives and health of Chinese people. With continuous breakthroughs in basic research and targeted treatment, the survival period of CLL/SLL patients has been extended, but there are still many challenges in treatment in this field, and there is an urgent need for new treatments with excellent efficacy and safety to be introduced.

APG-2575 is a novel oral Bcl-2 selective inhibitor independently developed by Yasheng Pharmaceutical. By selectively inhibiting Bcl-2 protein, it restores the normal apoptosis process of cancer cells, thus achieving the goal of treating tumors. APG-2575 has best-in-class potential at the global level. It is the second Bcl-2 inhibitor in the world and the first in China to see clear efficacy and enter a critical registered clinical stage. Currently, APG-2575 is undergoing multiple clinical studies worldwide, and more than 300 CLL/SLL patients have been treated with APG-2575.

Research shows that APG-2575 has strong monotherapy and combined treatment potential in CLL/SLL patients, and is a safer, more effective, and convenient treatment option.

It is worth mentioning that in August 2023, APG-2575 was approved by the US Food and Drug Administration (FDA) to conduct a globally registered phase III clinical study aimed at evaluating the efficacy and safety of APG-2575 combined with a BTK inhibitor in the treatment of CLL/SLL patients previously treated.

At present, clinical development of innovative Bcl-2 inhibitors by Yasheng Pharmaceutical is progressing steadily. First, as the first domestically produced Bcl-2 inhibitor, it was the first phase III clinical trial approved in the US to carry out last-line treatment. This time, it is also leading the advanced army in first-line treatment, establishing a leading position in Bcl-2 inhibitors. And as APG-2575 successfully enters the critical clinical phase, if it successfully passes clinical verification, it will soon provide new treatment options for CLL/SLL patients.

Furthermore, from the perspective of acotinib, which is currently being treated in combination with APG-2575, this product is a new generation of highly selective BTK inhibitors that can inhibit the BTK pathway and is highly selective, and has become the standard treatment for CLL patients worldwide. Acotinib received accelerated approval from the US FDA in 2017 for second-line treatment of mantle cell lymphoma (MCL), and expanded indications in 2019 to treat adult patients with CLL/SLL.

Up to now, acotinib has been approved for sale in more than 50 countries/regions, including the European Union and Japan. In China, two indications for acotinib have been approved one after another this year. They are used to treat MCL patients who have received at least one treatment in the past, and adult CLL/SLL patients who have received at least one treatment in the past.

The Zhitong Finance App learned that at the ASH conference in December 2022, Yasheng Pharmaceutical first disclosed clinical data on APG-2575+ acotinib combined treatment for CLL/SLL. As of December 5, 2022, 79 patients were enrolled in this combination therapy group. The data showed that the objective remission rate (ORR) of APG-2575+ acotinib treatment R/R CLL/SLL was as high as 98% (72/73), of which the ORR for 16 first-time patients was 100%. It is easy to see from this that compared with the clinical data of other Bcl-2+BTK combination treatments, the previously disclosed APG-2575+ acotinib combination treatment data is impressive, proving that it has the potential to become BIC.

Dr. Zhai Yifan, Chief Medical Officer of Yasheng Pharmaceutical, said, “The combined use of Bcl-2 inhibitors and BtK inhibitors has always been the focus of attention of academia and industry. Yasheng Pharmaceutical's Bcl-2 inhibitor APG-2575 is an important variety in the company's apoptosis pipeline. The global phase II study on CLL/SLL patients in combination with acotinib shows that this is a highly promising and truly patient-centered treatment strategy. Currently, CLL/SLL treatment abroad has moved into a new era without chemotherapy, and China also urgently needs a safer and more effective Bcl-2 inhibitor for combined treatment with BTK inhibitors. In the future, we will adhere to the mission of 'solving the unmet clinical needs of patients in China and the world', and work with AstraZeneca to actively promote the development of related clinical trials, promote APG-2575 to market as soon as possible, and benefit patients as soon as possible!”