Author: Li Aohua

On November 11, the concept of weight loss drugs rose collectively. The Wind weight loss drug index rose 3.14% overall, of which Borui Pharmaceutical (688166. SH) led the gainers, up 16.25%, while Sirnaomics (688117. SH), Nuotai Biotech (688076. SH) rose more than 7%, and Hanyu Pharmaceuticals (300199. SZ) rose more than 5%.

On the news side, it has recently been reported that the patent application for GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide) receptor dual agonist BGM0504 injection independently developed by Borui Pharmaceutical in the United States has been approved, laying the foundation for its "going overseas" strategy.

Times Finance called Borui Pharmaceutical Securities Department as an investor to verify the above news, and the relevant person replied that the company's announcement shall prevail, and if the news meets the disclosure standards, the company will issue an announcement.

According to the official website of the United States Patent and Trademark Office (USPTO), the patent application was updated on November 8 to "Notice of Allowance Data Verification Completed".

Feng Junjie, a partner of Guangdong Legal Shengbang Law Firm, told Times Finance that the examination process of U.S. invention patents generally includes preliminary examination and substantive examination, and after the preliminary examination is passed, the text of the patent application will be disclosed first, and then the substantive examination will be entered according to the application, and the substantive examination is mainly to evaluate whether the patent application is clear, whether it has novelty, inventiveness, implementability, etc., and to review whether the patent can be granted. Examiners at the substantive examination stage usually issue one or more office actions. According to the documents issued by the USPTO, "Notice of Allowance Data Verification Completed" means that the patent application has met the conditions for grant and is in the preparatory stage of grant.

Image source: PicWorm Creative

The chairman personally "brought the goods" and PK semaglutide head-to-head

The sales myth created by the GLP-1 continues.

With the disclosure of the third quarterly report of multinational pharmaceutical companies, the battle for the global "drug king" in 2024 is gradually becoming clear. According to Merck's 2024 Q3 report, Keytruda (pembrolizumab) continues to be firmly in the TOP1 of the world's best-selling drug list, with cumulative sales of more than $21.6 billion in the first three quarters.

According to Novo Nordisk's third quarterly report, semaglutide contributed a total of 141.213 billion Danish kronor sales to Novo Nordisk in the first three quarters, totaling about $20.2 billion. Another star weight-loss drug, Eli Lilly's GLP-1/GIP dual agonist tirpatide, is also growing at a rate that should not be underestimated. According to Eli Lilly's third quarterly report, in the first three quarters of 2024, tirpatide sales totaled $11 billion, and the drug was approved by the U.S. Food and Drug Administration (FDA) for hypoglycemic and weight-loss indications in 2022 and 2023, respectively.

The strong "wealth-making" ability of the GLP-1 track has naturally attracted countless players, including Borui Pharmaceutical.

According to Borui Pharmaceutical, BGM0504 can stimulate the downstream pathways of GIP and GLP-1, produce biological effects such as blood sugar control, weight loss and treatment of nonalcoholic steatohepatitis (NASH), showing the potential for the treatment of a variety of metabolic diseases.

BGM0504 "out of the circle" is inseparable from the "goods" effect of celebrities.

In October 2023, Yuan Jiandong, chairman of Borui Pharmaceutical, claimed in a conference call that he tried the company's product under development, BGM0504 injection, and in almost two months, his weight dropped from 91 kilograms to 76 kilograms. Under the publicity of the chairman's personal drug test, Borui Pharmaceutical rose to the limit the next day. However, a few days later, the Jiangsu Securities Regulatory Bureau decided to take administrative supervision measures against Yuan Jiandong by issuing a warning letter, and recorded it in the integrity file of the securities and futures market.

Although the above-mentioned "bringing goods" behavior has been punished by regulators, this does not affect Borui Pharmaceutical's high hopes for BGM0504.

According to the financial report, in the first three quarters of this year, Borui Pharmaceutical's R&D investment was about 222 million yuan, a year-on-year increase of 35.3%, mainly due to the company's adherence to the "R&D-driven" strategy and the continuous increase in R&D investment in innovative drugs and inhalation preparations such as BGM0504 injections.

Previously, Borui Pharmaceutical launched a "head-to-head" study of BGM0504 and semaglutide. In August this year, the data of the phase II clinical trial released by Borui Pharmaceutical showed that after 18 weeks of treatment, the BGM0504 (15mg group) had an average reduction of 2.76% compared with the baseline HbA1c (baseline mean glycosylated hemoglobin) compared with the placebo group, which was not only better than semaglutide under the same trial, but also better than the previous literature data of tirpatide.

On October 21, Borui Pharmaceutical announced that the phase III clinical trial protocol of BGM0504 injection for bariatric indications has successfully passed the review of the Ethics Review Committee of Peking University People's Hospital and obtained the corresponding ethical review approval.

GLP-1 patent disputes are surging

Behind the smoke of the R&D and sales war for GLP-1 drugs, a dispute over drug patents is also unfolding.

In the pharmaceutical industry, patent challenges are a common means of competition. In general, the patent term for a drug is 20 years. In order to fully protect their commercialization rights, original pharmaceutical companies will actively apply for patents at the R&D stage to protect their intellectual property rights. However, as the patent protection period expires, generic drug companies often launch patent challenges to seize market share as soon as possible.

It is understood that the patent protection period of the core sequence of semaglutide in China is expected to expire in 2026. In June 2021, Huadong Medicine (000963. Sino-US East China, a subsidiary of China and the United States, submitted an application for invalidation of the core patent of semaglutide to the State Intellectual Property Office. In September 2022, the State Intellectual Property Office ruled that the core patent CN200680006674.6 of semaglutide was invalid in its entirety, on the grounds that Novo Nordisk had not disclosed the experimental results data of the core compound. Novo Nordisk has now appealed to the Intellectual Property Tribunal of the Supreme People's Court, and the patent dispute has not yet been resolved.

In April this year, the marketing application of semaglutide injection "Jiyoutai" submitted by Jiuyuan Gene was accepted by the State Food and Drug Administration, which is the first domestic generic semaglutide to be declared for marketing. "Unless a court of competent jurisdiction finally rules that the patent is invalid, we will not be able to commercialize JY29-2 (Jiyoutai) before the expiration of the patent," Jiuyuan Gene said. ”

In view of the tense situation of the GLP-1 patent battle, Borui Pharmaceutical's investors were also worried about whether the BGM0504's patent application could be successfully implemented.

In August this year, Borui Pharmaceutical replied on the investor interactive platform that the company and its partners found an important contribution of key K20 residues to GLP-1R/GIPR agonistic activity through molecular dynamics simulation, which resulted in the BGM0504 of the modification strategy of new fatty acid side chains. BGM0504 molecular structure does not overlap with the molecular structure covered by Eli Lilly's tirpatide patent. The company has hired professional intellectual property firms at home and abroad to conduct several rounds of patent analysis, and after several rounds of analysis, the company confirmed that there is no risk of infringement in the patent. At present, the company's patents in China have been authorized.