Tides Therapeutics Files IPO Prospectus Highlighting Lilly-Backed Oral GLP-1 Small Molecule Candidate

On 2025-04-14, Pfizer announced the decision to halt the development of the oral GLP-1RA danuglipron (PF-06882961), which was under investigation for chronic weight management. In June 2023, Pfizer had also terminated the clinical development of another small-molecule GLP-1 receptor agonist, Lotiglipron.

Although Danuglipron (twice daily) showed good weight loss effects, it did not demonstrate a significant advantage. Moreover, the incidence of gastrointestinal reactions with Danuglipron (twice daily) was relatively high (nausea 73%, vomiting 47%, diarrhea 25%), and the discontinuation rate was also high (50%). For these reasons, Pfizer discontinued the twice-daily oral version of Danuglipron in July 2024 and shifted focus to developing its once-daily oral extended-release formulation.

On 2025-04-14, Innovent Bio's IBI362 injection (Masitide) registered a clinical trial (CTR20251394) in the CTR. This is a clinical study to evaluate the efficacy and safety of IBI362 in subjects with moderate to severe obstructive sleep apnea and obesity. The indication is moderate to severe obstructive sleep apnea with BMI ≥28kg/m².

This is a randomized, double-blind, placebo-controlled Phase III clinical study aimed at evaluating the efficacy and safety of IBI362 in Chinese subjects with moderate to severe obstructive sleep apnea and BMI≥28kg/m². The study plans to enroll 260 participants in China. The primary endpoint is the magnitude of change in AHI from baseline over 48 weeks.

On 2025-04-15, Paijin Biologics registered a clinical trial (CTR20251442) on the CTR platform for its Pegylated Peptide Injection for Thrombopoietin. This is a Phase Ib, single-arm, open-label, dose-escalation study evaluating the safety and efficacy of a single subcutaneous injection of Pegylated Peptide for Thrombopoietin (PN20) in patients with thrombocytopenia due to chronic liver disease.

The primary objective is to evaluate the safety and tolerability of a single subcutaneous injection of PN20 in patients with chronic liver disease-associated thrombocytopenia and to determine the recommended Phase II dose. The secondary objectives are 1) to assess the efficacy of a single subcutaneous injection of PN20 in patients with chronic liver disease-associated thrombocytopenia; 2) to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity characteristics of a single subcutaneous injection of PN20 in patients with chronic liver disease-associated thrombocytopenia.

On 2025-04-15, Gan&Lee Pharmaceuticals registered a clinical trial (CTR20251438) on the CTR platform for its GZR18 injection. This is a Phase I study to evaluate the pharmacokinetics and safety of GZR18 injection in subjects with renal impairment and those with normal renal function.

This is a non-randomized, open-label, single-arm trial. The primary objective is to evaluate the pharmacokinetic (PK) differences of GZR18 injection in subjects with renal impairment compared to subjects with normal renal function, providing a basis for developing clinical dosing regimens for patients with renal impairment.

On April 15, 2025, U.S. time, MetaVia (NASDAQ:MTVA) announced positive results for its obesity treatment candidate DA-1726 in the second part of a Phase 1 clinical trial (a 4-week multiple ascending dose study, MAD). The clinical progress is as follows:

- The trial results showed good safety and tolerability, with no serious adverse events or treatment interruptions;

- The 32 mg dose group achieved an average weight loss of 4.3% within 26 days, with a maximum of 6.3%;

-83% of patients experienced early satiety, indicating a therapeutic signal;

- No hypoglycemic side effects, and good blood glucose control, suggesting the indication can be expanded to diabetes;

- Waist circumference decreased by an average of 1.6 inches, with a maximum reduction of 3.9 inches, and showed good sustainability;

- The main adverse reactions are mild gastrointestinal reactions, most of which are relieved within 24 hours;

- Plan to enter subsequent clinical trials to compare the tolerability of Wegovy® in patients who dropped out early.

DA-1726 is a novel oxyntomodulin (OXM) analog and a once-weekly GLP1R/GCGR dual agonist, a peptide molecule that achieves weight loss and metabolic improvement by suppressing appetite and increasing energy expenditure. It also has the potential for treating MASH and type 2 diabetes.

MetaVia is a clinical-stage biotechnology company dedicated to treating cardiometabolic diseases (such as obesity, MASH, etc.).

On 2025-04-16, Shanghai Topgen Biotech and Shengdi Pharmaceutical's HRS-5817 Injection registered a clinical trial (CTR20251414) in the CTR. This is a Phase I study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single dose in healthy or obese subjects.

This is a randomized, double-blind, placebo-controlled, dose-escalation Phase I study. The primary objective is to evaluate the safety and tolerability of a single subcutaneous injection of HRS-5817. The secondary objectives are to assess the pharmacokinetic (PK) characteristics of a single subcutaneous injection of HRS-5817; to evaluate the pharmacodynamic (PD) characteristics of a single subcutaneous injection of HRS-5817; and to assess the immunogenicity profile of a single subcutaneous injection of HRS-5817.

HRS-5817 Injection is the fifth project jointly developed by Shanghai TopGene Biotech and Fujian Hengrui Biotechnology over the past two years. It belongs to the siRNA class of molecules.

On 2025-04-16, TG103 Injection from Shihai Group Baik (Shandong) Biopharmaceutical was registered for a clinical trial (CTR20251416) in the CTR. This is a Phase III clinical trial to evaluate the efficacy of TG103 Injection in treating overweight/obesity.

This is a randomized, double-blind, placebo-controlled, dose-escalation Phase III study. The primary objective of the study is to evaluate the effect of TG103 injection on body weight in non-diabetic overweight/obese subjects. Secondary objectives: To evaluate the safety, pharmacokinetic characteristics, and immunogenicity of TG103 injection in non-diabetic overweight/obese subjects.

TG103 is an innovative long-acting recombinant human GLP-1 Fc fusion protein, acting as a GLP-1 receptor agonist, with the ultra-long-acting potential of being injected once every two weeks.

On 2025-04-17, Takeda registered a clinical trial (CTR20251511) in the CTR for its injectable Teduglutide. This is an open-label, Phase 3 study evaluating the efficacy, safety, and pharmacokinetics of Teduglutide after 24 weeks of treatment in adult and pediatric Chinese subjects with short bowel syndrome.

This is a non-randomized, open-label, single-arm trial. The primary objective is to evaluate the efficacy of once-daily teduglutide administration over a 24-week treatment period in PS-dependent Chinese adult SBS subjects. Secondary objectives are as follows: pediatric subjects – to assess the efficacy of once-daily teduglutide administration over a 24-week treatment period in PS-dependent Chinese pediatric SBS subjects; adult and pediatric subjects – to evaluate additional efficacy parameters of teduglutide treatment based on the reduction in PS dosage in Chinese adult and pediatric SBS subjects, to assess the safety and tolerability of teduglutide treatment in Chinese adult and pediatric SBS subjects, and to study the pharmacokinetic characteristics of teduglutide treatment in Chinese adult SBS subjects; to evaluate the immunogenicity of teduglutide treatment in Chinese adult SBS subjects. The exploratory objective is to evaluate citrulline levels in Chinese adult SBS subjects after teduglutide treatment.

On 2025-04-17, Novo Nordisk registered a clinical trial (CTR20251468) in the CTR for NNC0519-0130 B 34 mg/mL. This is an investigational Phase I study of the new drug NNC0519-0130 in overweight male subjects in China, with the indication being type 2 diabetes.

This is a randomized, double-blind, placebo-controlled parallel study aimed to evaluate the pharmacokinetics, safety, and tolerability of multiple subcutaneous doses of NNC0519-0130 in overweight or obese but otherwise healthy male subjects in China.

NNC0519-0130 is a dual-target GIP/GLP-1 receptor agonist administered once weekly via subcutaneous injection. Previously, Novo Nordisk has initiated multiple Phase 1 and Phase 2 clinical studies on NNC0519-0130 injection in the United States, Japan, Australia, South Korea, and other regions, with plans to evaluate the pharmacokinetics, safety, and efficacy of NN0519-0130 in healthy individuals as well as those with type 2 diabetes and obesity.

On 2025-04-17, Novartis' radiopharmaceutical Gallium [68Ga] oxodotreotide injection preparation kit received clinical tacit approval from the CDE. After being radiolabeled with gallium-68, this drug can be used as a radioligand imaging agent to determine the SSTR-positive expression status in patients via positron emission tomography (PET), aiming to achieve patient screening.

On 2025-04-17, Lilly announced positive results from the Phase 3 clinical trial of ACHIEVE-1, which evaluated the safety and efficacy of the oral small-molecule GLP-1 receptor agonist Orforglipron compared to placebo in adult patients with type 2 diabetes whose blood sugar levels were inadequately controlled by diet and exercise alone. Orforglipron is the first oral small-molecule GLP-1RA, with no restrictions related to food or water intake, and has successfully completed its Phase 3 trial.

In the first Phase 3 clinical trial of the ACHIEVE project, orforglipron met the primary endpoint, showing a significantly greater reduction in glycated hemoglobin (A1C) at week 40 compared to the placebo group, with an average decrease of 1.3% to 1.6% from a baseline of 8.0% (using the efficacy estimand). For a key secondary endpoint, over 65% of patients receiving the highest dose of orforglipron achieved an A1C level ≤6.5%, below the diabetes threshold defined by the ADA. In another key secondary endpoint, patients treated with orforglipron at the highest dose experienced an average weight loss of 7.3 kg (7.9%). Given that patients had not yet reached a weight plateau by the end of the study, this may indicate that maximum weight loss has not been fully achieved.

Based on the analysis of the estimated treatment effects, all doses of orforglipron significantly reduced patients' A1C levels. Regarding the key secondary endpoint of weight change, the 12 mg and 36 mg doses also demonstrated statistically significant weight loss effects.

-A1C Reduction: 1.2% (3 mg), 1.5% (12 mg), 1.5% (36 mg), 0.4% (placebo).

- Percentage of weight loss: 4.5% (3 mg), 5.8% (12 mg), 7.6% (36 mg), 1.7% (placebo)

- Weight loss figures: 4.2 kg (9.3 lbs; 3 mg), 5.2 kg (11.5 lbs; 12 mg), 7.2 kg (15.8 lbs; 36 mg), 1.5 kg (3.4 lbs; placebo).

In the ACHIEVE-1 study, the overall safety profile of orforglipron was consistent with the established safety of GLP-1 class drugs. The most common adverse events were gastrointestinal-related and mostly mild to moderate. Common adverse events in the orforglipron groups (3 mg, 12 mg, and 36 mg) included: diarrhea (19%, 21%, 26%, vs. placebo 9%), nausea (13%, 18%, 16%, vs. placebo 2%), dyspepsia (10%, 20%, 15%, vs. placebo 7%), constipation (8%, 17%, 14%, vs. placebo 4%), and vomiting (5%, 7%, 14%, vs. placebo 1%). The proportions of treatment discontinuation due to adverse events were 6% (3 mg), 4% (12 mg), and 8% (36 mg), compared to 1% in the placebo group. No liver safety signals were observed.

The results of the ACHIEVE-1 study will be presented at the 85th ADA Scientific Sessions and published in a peer-reviewed journal. More results from the Phase 3 clinical trial program of the ACHIEVE studies, as well as the Phase 3 clinical trial results of orforglipron for weight management from the ATTAIN study, are expected to be released before the end of this year. Lilly anticipates submitting a marketing application for orforglipron for weight management to global regulatory authorities by the end of this year, with an anticipated submission for the treatment of type 2 diabetes by 2026.

On April 17, 2025, U.S. time, Endevica Bio announced that its candidate drug TCMCB07 (referred to as B07) had completed the first patient dosing in a Phase II clinical trial aimed at preventing weight loss in cancer patients undergoing chemotherapy. This clinical trial, conducted in collaboration between Endevica Bio and WuXi Clinical, plans to recruit 100 patients with Stage IV metastatic colorectal cancer across 20 clinical sites. The goal is to reduce weight loss and delay or prevent the onset of cachexia by intervening with B07 early in the patients' chemotherapy.

B07 is a melanocortin-3/4 receptor antagonist peptide drug that has the ability to cross the blood-brain barrier and can modulate the body's metabolic and behavioral responses to chronic diseases. In earlier animal studies and Phase I clinical trials, B07 demonstrated good safety, lean body mass preservation, and appetite improvement effects.

On 2025-04-18, the domestic generic drug application for Xiantong Pharmaceutical's Class 3 radioactive therapeutic drug, Lutetium [177Lu] Oxytocin Injection, was accepted by the CDE.

On 2025-04-18, Huayi Technology's copper [64Cu] oxytocin octreotide injection received clinical tacit approval from the CDE. This drug is a radioactive diagnostic agent that, when used in conjunction with positron emission tomography (PET), can be used for lesion localization in adult patients with somatostatin receptor-positive neuroendocrine tumors (NETs).

On 2025-04-18, Novartis' Lutetium [177Lu] oxodotreotide injection received clinical tacit approval from the CDE. This drug can be used for newly diagnosed Grade 1 and Grade 2 (Ki-67 < 10%) advanced GEP-NET patients with a high disease burden.

2025-04-18, Beijing Zhide Peptide's semaglutide injection was registered for a clinical trial (CTR20251508) on the CTR platform. This is a clinical study evaluating the efficacy and safety of semaglutide injection compared with Wegovy®. The indication is obesity.

On April 21, 2025, U.S. time, clinical-stage biotechnology company Coya Therapeutics (NASDAQ: COYA) announced that its investigational candidate drug COYA 303 demonstrated significant enhancement in the function of regulatory T cells (Tregs) and extended their viability in an in vitro model of human immune cells. The relevant study has been published in the journal *NeuroImmune Pharmacology and Therapeutics*.

COYA 303 is a combination biologic consisting of low-dose interleukin-2 (LD IL-2, COYA 301) and a GLP-1 receptor agonist (GLP-1RA), designed to treat autoimmune and neurodegenerative diseases through multi-target immune modulation. In in vitro experiments, COYA 303 increased the suppressive effect of Tregs on pro-inflammatory myeloid cells to 42% (p < 0.001), significantly higher than using LD IL-2 (15%) or GLP-1RA (20%) alone; meanwhile, COYA 303 significantly inhibited the apoptosis pathway of Treg cells, reducing the expression level of the pro-apoptotic factor BAX (p < 0.01), suggesting its support for Treg survival in inflammatory environments.

The synergistic effect of COYA 303 is expected to open new therapeutic directions in inflammation-driven neurodegenerative diseases such as Alzheimer's disease.

On 2025-04-15, Cyprumed GmbH, a drug delivery company specializing in innovative oral peptide formulations, announced a non-exclusive license and option agreement with MSD. The two parties will collaborate to leverage Cyprumed's advanced delivery technology to jointly develop MSD’s oral peptide drugs. This collaboration signifies an upcoming breakthrough in the field of oral peptide therapies, offering patients more convenient medication options.

Under the terms of the agreement, MSD obtained non-exclusive global rights to Cyprumed’s oral peptide delivery platform for an undisclosed number of targets. The agreement also grants MSD an exclusive option to license Cyprumed’s technology for a single target. Cyprumed is eligible to receive up to $493 million in upfront, development, regulatory, and net sales milestones related to the approval of any products under the collaboration. If MSD exercises its exclusive licensing option, Cyprumed may receive additional payments. MSD will be responsible for the research, development, manufacturing, and commercialization of any products using Cyprumed’s delivery technology under the agreement.