AI-Discovered Natural Peptide BRP Shows Semaglutide-Comparable Efficacy with Improved Safety Profile

On 2025-03-03, Yinnuo Pharma registered a Phase IIb clinical trial for "Suparutide Injection" for overweight and obesity on the China Drug Clinical Trial Registration and Information Platform (CTR).

Supaglutide is China's first independently developed new-generation humanized ultra-long-acting GLP-1 receptor agonist, with active R&D efforts underway in the fields of type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH) among other metabolic diseases.

On March 3, 2025, the Clinical Trial website showed that Novartis had initiated the Phase III clinical trial (AcTFirst) of the next-generation radioligand therapy (RLT) AAA817 ([225Ac]Ac-PSMA-617).

This study is a multicenter, randomized, open-label, active-controlled clinical trial (n=486) designed to evaluate the efficacy and safety of AAA817 in combination with an androgen receptor signaling pathway inhibitor (ARPI) compared to investigator’s choice of standard of care (SoC) in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) patients who have not received taxane-based chemotherapy or RLT. The primary endpoint of the study is radiographic progression-free survival (rPFS).

AAA817 is an α-particle radiopharmaceutical acquired by Novartis after purchasing Endocyte. Compared to β particles, α particles possess higher linear energy transfer (LET) and a shorter range, which can effectively enhance the killing power and precision of RLT on tumors while reducing systemic side effects.

On 2025-03-04, Shengdi Pharma, a subsidiary of Hengrui Pharma, registered "HRS9531 Injection" (CTR20250659) for clinical trials on diabetes and weight loss in the CTR.

HRS9531 Injection is a GLP-1/GIP dual receptor agonist independently developed by Hengrui Pharma. The 8mg dose significantly reduced body weight in the Phase II clinical trial for weight loss (HRS9531-203) while demonstrating good safety and tolerability.

On March 5, 2025, the Clinical Trial website showed that Amgen had initiated two Phase III clinical trials (MARITIME-1 and MARITIME-2) for AMG 133 (Maridebart Cafraglutide, MariTide), marking the entry of AMG 133 into the Phase III development stage.

AMG133 is a first-in-class antibody-peptide conjugate drug independently developed by Amgen, which can be administered once every 4 weeks. It consists of a fully human monoclonal antibody targeting GIPR conjugated with two GLP-1 analogs, and functions by inhibiting GIPR and activating GLP-1R to reduce food intake, regulate metabolism, thereby achieving weight loss and lowering blood glucose.

On March 6, 2025, AstraZeneca registered a Phase 2b clinical trial on Clinicaltrials.gov for the combination therapy of AZD9550 + AZD6234 for weight loss. The primary endpoints of this Phase 2b clinical trial are the percentage of weight loss after 36 weeks of treatment and the proportion of patients who lose more than 5% of their body weight.

AZD9550 is a GLP-1/GCG dual-target agonist, which previously underwent a Phase I clinical trial for MASH. AZD6234 is a long-acting Amylin analog, which previously underwent a Phase II clinical trial for weight loss as a monotherapy.

Novo Nordisk clarified that the current clinical research of its GLP-1 drugs in the addiction field is limited to an ongoing Phase II trial. This trial tests semaglutide and two other drugs, with alcohol use as a secondary endpoint. The global Phase II trial, initiated in May 2024, investigates the efficacy of semaglutide, cagrilintide (an amylin analog), and NNC0194-0499 (an FGF21 analog) used alone or in combination in patients with alcoholic liver disease. Liver injury treatment is the primary endpoint, while alcohol consumption is a secondary endpoint.

Novo Nordisk has also made progress in other neurological studies related to GLP-1. In October 2024, a real-world study showed that semaglutide could reduce the risk of Alzheimer's disease by 40% to 70% in patients with type 2 diabetes. Currently, the company is conducting two Phase III clinical trials (EVOKE and EVOKE Plus) to formally evaluate the efficacy of semaglutide in patients with Alzheimer’s disease, with results expected to be announced in September 2025.

ITM Presents Positive Data from Phase III COMPETE Trial at ENETS 2025: ITM-11 (n.c.a. 177Lu-edotreotide) Shows Promising Results in Targeted Radiopharmaceutical Therapy for Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumor Patients

Phase 3 COMPETE Trial Results Show n.c.a. 177Lu-edotreotide Significantly Extended Progression-Free Survival (PFS) in Patients with Grade 1 or 2 Somatostatin Receptor-Positive Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) Compared to Everolimus. The median PFS for 177Lu-edotreotide was 23.9 months versus 14.1 months for everolimus (p = 0.022). The trial enrolled 309 patients, showing a lower incidence of adverse events in the 177Lu-edotreotide group (82.5%) compared to 97.0% in the everolimus group.

Although the interim overall survival (OS) data did not reach statistical significance, 177Lu-edotreotide showed a favorable trend (63.4 months vs. 58.7 months in the everolimus group). The company plans to submit a New Drug Application (NDA) to the FDA in 2025. These findings make 177Lu-edotreotide a promising new treatment option for patients with progressive, inoperable GEP-NETs.

Stanford Medical School Researchers Discover BRP, a Natural Peptide Molecule with Potential as an Alternative to Semaglutide for Weight Loss. Advantages of BRP include: 1) Significant weight loss without side effects: appetite suppression and weight reduction without common semaglutide side effects such as nausea and constipation; 2) More precise mechanism of action: BRP primarily targets the hypothalamus (the central regulator of appetite and metabolism) in the brain, while semaglutide acts on the brain, intestines, and pancreas; 3) Potent neuronal activation: BRP is derived from the prohormone BRINP2 and exhibits 10 times stronger activation of neuronal activity compared to GLP-1.

This study combines AI screening with the Peptide Predictor algorithm to identify BRP from 373 candidate peptides, improving screening efficiency. In lean mice and minipig experiments, food intake decreased by 50% within one hour after BRP injection. Obese mice injected daily with BRP lost approximately 3 grams of weight over 14 days, primarily due to fat reduction, with no significant discomfort, reduced activity, or changes in water consumption.

On 2025-03-10, a BioSpace report highlighted concerns over side effects of GLP-1 weight-loss drugs, with complex and varied reasons leading to patient discontinuation. Despite the significant weight-loss efficacy of GLP-1 drugs such as Novo Nordisk's Wegovy and Eli Lilly's Zepbound gaining attention, their common gastrointestinal side effects—such as nausea, vomiting, diarrhea, constipation, and abdominal pain—occur in 40% to 70% of patients, becoming a major factor for discontinuation.

To Reduce Discontinuation Rates, Pharmaceutical Companies and Doctors Are Actively Collaborating to Improve Patient Tolerance Through Dose Adjustments, Combination Therapies, and Complementary Medications. For Example, Zepbound Combines GLP-1 with GIP to Partially Alleviate Gastrointestinal Discomfort. Additionally, Some Companies Are Developing Adjunctive Drugs Targeting Side Effects, Such as Mytesi, a Plant-Based Oral Medication Developed by Napo Pharmaceuticals (a Subsidiary of Jaguar Health), Which Has Been Approved for HIV-Related Diarrhea and Shows Potential in Relieving Abdominal Pain, Bloating, and Constipation.

However, the reasons for discontinuing GLP-1 drugs are not limited to side effects. Studies show that patients discontinue the medication due to a variety of factors, including drug cost, supply shortages, physician recommendations to switch medications, and achievement of weight management goals. A real-world study from July 2024 indicated that 85% of patients discontinued the treatment within two years of starting, but only 5% did so because of side effects.

On 2025-03-03, the CDE official website showed that "HDM1005 Injection" from Sino-US East China Pharmaceutical has received the clinical trial tacit approval from CDE. It is intended for the treatment of adult patients with heart failure with preserved ejection fraction (HFpEF) combined with obesity or overweight.

HDM1005 Injection is a long-acting dual agonist targeting both the human GLP-1 receptor and GIP receptor in the peptide class. Preclinical studies have shown that HDM1005 promotes the production of cyclic adenosine monophosphate (cAMP) by activating the GLP-1 receptor and GIP receptor, increases insulin secretion, suppresses appetite, delays gastric emptying, and improves metabolic function, thereby improving plasma volume, reducing oxidative stress and systemic inflammation, and enhancing cardiovascular adaptability. It has the effects of lowering blood glucose, reducing weight, and improving MASH as well as heart failure with preserved ejection fraction (HFpEF). Meanwhile, existing data indicate that HDM1005 demonstrates favorable drug-like properties and safety.

On March 3, 2025, the clinical trial applications for [225Ac]Ac-PSMA-617 Injection and Gallium [68Ga] Gozetotide Injection Kit, both Class 1 radiopharmaceuticals developed by Novartis, received tacit approval from the Center for Drug Evaluation (CDE) for clinical trials. The [225Ac]Ac-PSMA-617 Injection has been approved to conduct clinical research on "PSMA-positive metastatic castration-resistant prostate cancer that has progressed during or after [177Lu]Lu-PSMA-targeted therapy." After being radiolabeled with 68Ga, the Gallium [68Ga] Gozetotide Injection Kit becomes a radiotracer used to identify prostate-specific membrane antigen (PSMA)-positive lesions in adult prostate cancer patients through positron emission tomography (PET).

On March 4, 2025, the clinical trial application for MWN109 tablets by Minwei Biotech was accepted by the NMPA.

MWN109 is a fatty acid chain-modified peptide drug targeting GIP/GLP-1/GCG, aimed at treating type 2 diabetes, obesity, and overweight issues.

On March 5, 2025, the Goserelin Acetate Active Pharmaceutical Ingredient (API) independently developed by Zhong肽 Biochemical officially passed the individual review by the CDE and received marketing approval. According to the information disclosed on the CDE’s API and excipient registration platform, the registration status of this API has been updated to "A," indicating that it complies with GMP requirements and can be legally used in drug product manufacturing. To date, Zhong肽 Biochemical is the only company in China to have obtained marketing approval for Goserelin Acetate API.

Goserelin acetate is a gonadotropin-releasing hormone agonist (GnRH-a) that continuously stimulates the pituitary gland, causing a transient increase followed by a decrease in gonadotropin secretion, ultimately suppressing ovarian and testicular function and reducing estrogen or testosterone levels. It is widely used in cancer treatment and gynecological diseases.