ApicHope Pharma has submitted the IND application for an oral small molecule GLP-1R agonist APH01727 for patients with type 2 diabetes and obesity in China. ApicHope Pharmaceutical founded by Li Hanxiong engages in the research and development, production, and sales of traditional Chinese medicine products, chemical medicine, and biological vaccines.
| Li Hanxiong |
APH01727
In the press release issued by ApicHope, it was stated that APH01727 is intended to be a daily dose small molecule GLP-1 receptor agonist.
In 2022, ApicHope filed a patent （WO2024046342） covering the benzo bicyclic compounds aimed at treating GLP-1 receptor agonist-mediated diseases and/or disorders. The patent indicates that compound 4 has an EC50 value of approximately 0.08 nM, demonstrating significantly higher potency compared to danuglipron, which has an EC50 of around 13 nM.
| Compounds in the patent |
Oral GLP-1R Agonists in China
Although Pfizer and vTv (Huadong) terminated their oral small molecule GLP-1R agonists program last year, the story of Danuglipron (Pfizer) continues. Meanwhile, Lilly's Orforglipron is currently being evaluated in phase 3 trials for patients with obesity and diabetes. In China, the followers are coming.
| Oral GLP-1RA Landscape |
RGT-075 is a small molecule GLP-1R agonist developed by Regor Pharma, currently under phase 2 study in patients with obesity. In 2023, Regor terminated the phase 2 trial (NCT05297045) of RGT-075 in patients with type 2 diabetes due to financial constraints. However, last month, they initiated the phase 2 study for the treatment of obesity, with topline results expected to be announced in the second half of 2024.
In 2022, Regor presented the results of the phase 1 study in healthy adults. "The mean elimination half-life (t1/2) (from 6.3 to 11.7 hours) indicated suitability for QD dosing."
HRS-7535
In February 2023, Hengrui initiated the first phase 2 study of HRS-7535, a small molecule GLP-1R agonist, in China. Currently, HRS-7535 is being evaluated in two phase 2 trials for the treatment of diabetes and obesity.
At the end of 2023, Hengrui reported the results of the phase 1 trial, indicating that "HRS-7535 exhibited a safety and tolerability profile consistent with other GLP-1RAs and showed pharmacokinetics suitable for once-daily dosing." During multiple ascending dose (MAD) cohorts, subjects administered HRS-7535 experienced a mean reduction in body weight of 4.38 kg from baseline within 4 weeks.
HDM1002
HDM1002, a GLP-1R agonist developed by Huadong Medicine, has halted the development of TTP273 in China. Currently, HDM1002 is being investigated in a phase 2 trial, administered twice daily, for overweight patients.
Huadong Medicine presented the outcomes of a preclinical study at the EASA Annual Meeting in 2023. The in vivo study revealed that HDM1002 exhibits a potent hypoglycemic effect even at low doses.
GSBR-1290
GSBR-1290, an oral small molecule GLP-1RA developed by Structure Therapeutics in China, is currently undergoing evaluation in a phase 1/2 study targeting overweight and diabetes.
In December 2023, Structure Therapeutics shared the findings of the phase 2a study conducted on patients with diabetes and obesity. In the Type 2 Diabetes cohort, there was a notable reduction in HbA1c levels, with a statistically significant difference ranging from -1.01% to -1.02% when compared to the placebo at Week 12. Additionally, the study exhibited a significant and clinically meaningful weight reduction ranging from -3.26% to -3.51% at Week 12, also when compared to the placebo. The trend of weight loss continued to progress through Week 12. Furthermore, interim analysis results from the obesity cohort demonstrated a statistically significant and clinically meaningful weight reduction of -4.74% at Week 8, again compared to the placebo.
ECC5004
ECC5004 is a small-molecule glucagon-like peptide 1 receptor agonist drug being developed by Eccogene to treat cardiometabolic conditions like obesity, type-2 diabetes, and non-alcoholic steatohepatitis (NASH).
In 2023, AstraZeneca licensed in the global right of ECC5004 with an initial upfront payment of $185m.
XW-014
XW014, a small molecule GLP-1 receptor agonist developed by Sciwind Biosciences, is being positioned for potential oral once-daily dosing. It's scheduled to commence clinical trials in the first half of 2022.
During the EASL 2022 event, Sciwind presented findings from a preclinical study. This study revealed notable body weight reduction and decreased food intake at doses of 30 and 60 mg/kg BID of XW014 when compared to a vehicle.
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