Author: Deng Yuchen

From U.S. stocks to A- shares, global stock markets are reveling in the GLP-1 targets behind new weight-loss drugs.

The first week of A- shares closed in October, with the three major indexes remaining weak and volatile. By the close of trading on October 13, the Shanghai index was down 0.64 per cent, the Shenzhen Composite Index was down 0.99 per cent and the GEM index was down 1.11 per cent. However, GLP-1 concept stocks rose against the market, with Borui Pharmaceuticals (688166.SH), Baihua Pharmaceuticals (600721.SH), Zhongsheng Pharmaceuticals (002317.SZ) and other stocks up and down, Lepu Pharmaceuticals (300003.SZ), Changshan Pharmaceuticals (300255.SZ) and others up more than 10%.

The GLP-1 concept of US stocks has also performed well. According to Snowball data, the pharmaceutical giant Novo Nordisk (NVO.NYSE) rose 1.36 percent to close at $100.18 per share, with a total market value of $447.93 billion. On the 12th, it reached $102.06 per share, a record high.

According to market news, at the "Big Cafe Interpretation of the GLP-1 Industry Chain Series Exchange Conference" recently held by Founder Securities, Yuan Jiandong, chairman of Borui Pharmaceuticals, said that he had personally experienced the company's GLP-1 products. For two months, (weight) dropped from 91kg to 76kg ". The products used by Yuan Jiandong have completed Phase 1 clinical trials.

On October 13, a reporter from Times Weekly called the Borui Pharmaceutical Securities Department several times, but it was not connected as of press time. According to the interface news, the relevant staff of Borui medicine responded that the company's products are still in the research and development stage, and the individual situation can not represent the clinical trial data.

source: Borui biological official website

A-share "dual-target" innovative drugs get attention

After the market on October 13, Borui Pharmaceuticals issued a stock trading risk warning announcement, saying that the company's share price has risen 57.91 percent since September 25, 2023, higher than the industry's rise and the 50 index's rise over the same period.

In the risk warning, Borui Pharmaceuticals said that the company's GLP-1 product BGM0504 injection is still in the research and development stage. As of the disclosure date of the announcement, the two indications for weight loss and type 2 diabetes treatment have only obtained ethical approval for phase II clinical trials, of which phase II clinical treatment of type 2 diabetes has begun to be included. After the completion of the phase II clinical trial, it is necessary to confirm the confirmatory clinical trial scheme by the State Drug Administration, carry out and complete the phase III clinical study, and be reviewed and approved by the State Drug Administration before production and listing.

"The research and development cycle of innovative drugs is long, the investment in research and development is large, and the enrollment of various clinical studies and the implementation of research protocols are affected by a variety of uncertain factors, and there is a risk that the results of clinical studies may not be as good as expected or even fail." Borui Pharmaceuticals said in the announcement.

in the investor relations record disclosed on October 12, the relevant person in charge of borui pharmaceutical said in reply to a number of investment institutions that BGM0504 injection is a dual agonist of GLP-1 and GIP receptor independently developed by the company. Considering that GLP-1 overactivation is prone to a series of related side effects, the company reduced GLP-1 activity, but increased GIP activity to balance some of the side effects of GIP.

The design of the GLP-1/GIP dual target is the same mechanism as that of Lilly. NYSE's (Tirzepatide) and will also be compared by the market. In this regard, Borui Pharmaceuticals said that the company found that there is room for improvement in the side chain structure and connection site of GLP-1 and GIP dual target molecules, and believes that it can try to provide drug activity and improve pharmacokinetic characteristics by optimizing the side chain structure and adjusting the side chain modification site.

according to the disclosure of borui medicine, the average body weight of BGM0504 injection at the end of the follow-up (day 8/15) at the dose of 2.5-15mg decreased by 3.24-8.30% compared with the baseline period.

In addition to Borui Pharmaceuticals, Zhongsheng Pharmaceuticals also has a GLP-1/GIP dual-target drug. In its 2023 semi-annual report, the company's research on RAY002 is a long-acting GLP-1 class of innovative structural polypeptide drugs, with GLP-1 receptor and GIP receptor dual agonist activity. "In preclinical studies, the pharmacokinetic profile of RAY002 is significantly better than that of the same target compound. Phase I clinical studies are currently underway, and the first case was completed in May." The sentient beings pharmaceutical said.

"Multi-target and long-term development is currently the main direction of GLP-1 innovative drug research and development, but it must be pointed out that the current research and development of GLP-1 is still in a very early stage, and the current clinical data does not have a clear direction. It is still unknown which one can run out." October 13, a pharmaceutical industry investors told the times weekly reporter.

The joys and worries of "universal target"

While R & D is accelerating, GLP-1 is also showing greater market potential in reducing blood sugar and weight loss, and is known as the "universal target".

GLP-1 acts primarily by increasing insulin release, decreasing glucagon release, delaying gastric emptying, and decreasing appetite, thereby reducing body weight in certain patients, as well as reducing blood glucose levels and reducing the risk of major cardiovascular events such as heart attack or stroke in patients with type 2 diabetes.

on October 10, local time, Novo Nordisk announced that the phase III clinical study FLOW of GLP-1 drug semaglutide in the treatment of patients with type 2 diabetes and chronic kidney disease complicated with renal insufficiency was terminated early because the independent data monitoring committee (IDMC) analyzed the medium-term data and the efficacy of the drug had reached specific preset standards.

The FLOW study was initiated in 2019 with 3534 patients enrolled in 28 countries. Novo Nordisk said the clinical results are still blinded to the company, and the data is expected to be read out in the first half of 2024.

Previous papers have pointed out that GLP-1 may be used to treat Alzheimer's disease. Novo Nordisk will launch two Phase III trials in 2021 to study the efficacy of semaglutide in approximately 3700 patients with early Alzheimer's disease. It is understood that the trial is currently underway and the clinical trial is expected to be completed in September 2025.

The experimental efficacy of GLP-1 in the treatment of obesity and nonalcoholic steatohepatitis (NASH) has been quite successful compared to Alzheimer's disease.

According to Lilly's new three-receptor agonist Retatrutide data disclosed at the American Diabetes Association (ADA) annual meeting in June 2023, the drug is not only excellent in weight loss, but also shows a strong liver fat reduction effect. At the Retatrutide 8mg and 12mg therapeutic doses, the average relative liver fat reduction rate of subjects was> 80%. More than 80% of patients achieved fat reduction rate ≥ 70%. And more than 85% of patients lost liver steatosis at 48 weeks.

But GLP-1 is not perfect ". According to an article published in October by CCTV Finance and the Journal of the American Medical Association, an internationally renowned medical journal, compared with the incidence of serious side effects of another type of weight loss drug, bupropion/naltrexone, the use of GLP-1 weight loss drugs The risk of gastric paralysis has increased nearly 4 times, the risk of pancreatitis has increased 9 times, and the risk of intestinal obstruction has increased 4 times.

It is undeniable that the GLP-1 market is gradually being opened. According to Morgan Stanley's estimation, by 2030, the market size of obesity drugs alone is expected to exceed US $54 billion (contract RMB 384.8 billion), and GLP-1 is also expected to surpass PD-1/PD-L1 to become the largest category in the global market, reaching the top of the new generation of "drug king.