BEIJING – Shandong, China-based Luoxin Pharmaceuticals Group Stock Co. Ltd. said its PIK3α inhibitor, LX-086, has been approved by China’s National Medical Products Administration (NMPA) to enter clinical trials for advanced solid tumors, two weeks after Novartis AG’s alpelisib, which aims at the same target, was also granted IND clearance in China.

Developed internally by Luoxin, LX-086 will be investigated for use in treating advanced solid tumors carrying mutations or amplifications of the PIK3CA gene. The trial approval was granted by default 60 days after the company filed for an IND application.

According to Luoxin, preclinical data indicated that the drug candidate has a favorable enzymatic and cytological activity in vitro. In various solid tumor cells and animal models carrying mutations or amplifications of the PIK3CA gene, LX-086 showed a clear mechanism of action and exhibited significant antitumor activity.

The drug developer added that the compound showed good druggability and safety, and it plans to develop it for various advanced solid tumors – breast cancer, ovarian cancer, gastric cancer and liver cancer – carrying the PIK3CA mutation.

“Unlike conventional pan-PI3K inhibitors, LX-086 specifically acts on the PI3K protein alpha subunit with better targeting,” said Luoxin. It added that LX-086 can inhibit the excessive proliferation of tumor cells by inhibiting the PI3K-Akt-mTOR signaling pathway to achieve the purpose of treating various solid tumors, and at the same time avoid affecting the normal function of other subunits of the PI3K protein, thereby minimizing safety risks.

“Currently, China has yet to approve any PIK3A inhibitors; hence, the drug candidate carries great prospects in clinical application,” the company added.

LX-086 is the latest candidate that entered China’s clinical catch-up for PIK3α inhibitors. On April 27, Novartis’ BYL-719 (alpelisib) was granted IND approval by the NMPA to begin clinical trials in combination with fulvestrant in postmenopausal women and men with PIK3CA-mutated hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer.

Outside of China, alpelisib has gained marketing approval as Piqray by the FDA in May 2019. Bayer AG’s Aliqopa (copanlisib) and Verastem Inc.’s Copiktra (duvelisib) are two other PI3K inhibitors approved in the U.S.

Luoxin’s management was not immediately reachable to comment on its plan for LX-086’s clinical trials, but an investor relations officer told BioWorld that the company has a slew of innovative drugs in its pipeline.

Established in 1988, Luoxin focuses on developing gastrointestinal, respiratory and oncology drugs. It has made public announcements on 10 innovative drug candidates that aim at digestive system disorders and oncology: five are in clinical development, two are in IND-enabling stage and three are in preclinical studies.

Its most advanced innovative drug candidate is LXI-15028 (tegoprazan), a p-CAB inhibitor in-licensed from South Korean firm CJ Health Care Corp. It is now in phase III trials.

Also in its pipeline are plecanatide, in-licensed from Synergy Pharmaceuticals Inc., for treating adults with chronic idiopathic constipation and irritable bowel syndrome with constipation; mTORC1/2 inhibitor LXI-15029 for advanced malignant solid tumors; and oral selective estrogen receptor degrader LX-039 for estrogen receptor-positive breast cancer.

PI3K development in China

More than 10 Chinese pharmaceutical companies are developing PI3K drugs, but most of those are delta-directed.

In the same category as LX-086 is Haihe Biopharma Co. Ltd.’s CYH-33, co-developed with Shanghai Institute of Materia Medica at Chinese Academy of Sciences. CYH-33 was the first PIK3α inhibitor to enter the clinic in China, with the first patient dosed in July 2018. Meanwhile, Shanghai Junshi Biosciences Co. Ltd. and Risen (Suzhou) Pharma Co. Ltd.’s JS-105 is believed to be in preclinical stage.

As for PI3Kδ inhibitors, Innovent Biologics Inc.’s parsaclisib in-licensed from Incyte Corp., started patient dosing in a pivotal phase II registrational trial in China in April. The trial is to evaluate the efficacy and safety of parsaclisib in patients with recurrent or refractory follicular lymphoma or marginal zone lymphoma.

Also in phase II trials are Shanghai Yingli Pharmaceutical Co. Ltd.’s YY-20394 for relapsed/refractory follicular non-Hodgkin lymphoma, as well as Nanjing Sanhome Pharmaceutical Co. Ltd.’s SHC-014748M for relapsed/refractory indolent B-cell hematologic malignancies.

Meanwhile, Verastem’s Copiktra, in-licensed to China by CSPC Pharmaceutical Group, is in a China bridging trial that began in January for relapsed or refractory follicular lymphoma. A dual PI3K/HDAC inhibitor developed by Guangzhou Bebetter Medicine Technology Co. Ltd., BEBT-908, is also undergoing phase II trials.

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