Daewon oral semaglutide tablet DW5324 beats Rybelsus exposure in two small studies

Daewon oral semaglutide work has moved from the lab bench to a scientific meeting. Daewon Pharmaceutical, a South Korean drugmaker, says its tablet candidate DW5324 produced higher blood levels of semaglutide than Novo Nordisk's Rybelsus in two small human studies, with total exposure up to 3.14 times greater. The company is presenting the data at the AAPS PharmSci 360 meeting in New Orleans this week. The figures come from the company and have not appeared in a peer reviewed journal. They matter to makers because a peptide tablet loses most of its drug substance in the gut.

What Daewon reported from two crossover studies

The company ran two pharmacokinetic crossover studies that compared its formulation with a Rybelsus tablet, according to Korea Biomedical Review. In a crossover design each volunteer takes both products in turn, so every person serves as their own comparison. The studies enrolled 18 and 19 participants. Daewon said the area under the curve, a measure of total exposure over time, ranged from 1.90 to 3.14 times the Rybelsus value. Peak plasma concentration was up to 2.90 times higher, the company said. It did not say how much semaglutide each DW5324 tablet held, how the results varied between people, or which of the two studies produced the top figure. Those details decide whether the gain is a stronger tablet or simply a bigger one.

The preclinical numbers point the same way. In a parallel artificial membrane permeability assay, a lab test that models how a compound crosses a lipid barrier, the formulation showed up to 6.00 times the permeability of a control, the company said. In a single dose study in beagle dogs, exposure rose by up to 6.41 times. Animal and membrane results often shrink once a product reaches people, and here the human gain was about half the dog figure. The studies measured blood levels only. Daewon has not reported effects on blood sugar or weight, safety findings, or how the tablet behaves with food and water. For now the data show a formulation that gets more peptide into the blood in small groups, which is a necessary first step and not proof of a medicine.

How the polymer and lipid platform works

Daewon says DW5324 rests on an oral delivery platform it built in house from a complex of polymer and lipid. According to the company, the mix shields the peptide inside the digestive tract, controls when it is released, and helps it pass through the lining of the gut. That is a different approach from Rybelsus. The Rybelsus prescribing information says the tablet is made with salcaprozate sodium, known as SNAC, an absorption enhancer, and that semaglutide is taken up mainly in the stomach. Daewon has not said where along the gut its tablet releases the drug. Nor has it named the polymer or the lipid, which is normal for a platform it hopes to license to other companies.

Daewon has not said where along the gut its tablet releases the drug.

Kim Joo-il, who heads research and development at Daewon, linked the design to intellectual property as well as biology. The presentation will show that the platform "can solve both the patent barrier and the absorption rate limits of oral peptides at the same time," he said in the company's statement. The patent remark matters for trade. Novo Nordisk built its tablets around SNAC, so a rival that wants an oral semaglutide without waiting for every related right to lapse needs a different carrier. Daewon did not say which patents it has in mind or whether its own platform is patented in Korea or abroad. Kim also said the company aims to expand the platform to other biologic drugs and to export the technology through deals with global partners.

Why tablet exposure sets the drug substance bill

The label explains why a better carrier is a manufacturing question. It puts the absolute bioavailability of Rybelsus at about 0.4 to 1 percent, which means that well over 99 percent of the semaglutide in each tablet never reaches the bloodstream. A weekly injection skips the gut entirely, so a daily tablet needs far more drug substance per patient for the same effect. Novo has already shown what a better formula does to that bill. The same label covers newer Ozempic tablets with absolute bioavailability of about 1 to 2 percent, and it reports no clinically significant difference in exposure against Rybelsus even though each matching strength holds less semaglutide.

If DW5324 keeps its advantage in larger trials, a tablet could in principle reach the target blood level with less semaglutide inside it. That would cut the amount of peptide a maker has to synthesise and purify for every patient, which is where much of the cost sits, as our process coverage shows. Daewon has not made that claim. It has not said whether it will lower the amount per tablet, keep the amount and seek a stronger effect, or where its semaglutide comes from. The company does not report its own peptide plant for this program. Until it names a supplier and a target strength, the supply effect stays a possibility rather than a plan.

What Daewon oral semaglutide plans leave open

The next steps are company plans. Daewon said it will refine the formulation after the meeting and intends to ask Korean regulators in 2027 to clear a Phase 1 study, through an investigational new drug filing. Separately, it wants to license the platform to large drugmakers. A Phase 1 trial would test safety and drug levels in more people, and only later trials could show whether the higher exposure turns into better control of blood sugar or weight. The timeline puts any product years away. Daewon has not given a budget, a partner, or a manufacturing route for clinical supplies, and the company has not said whether it would make tablets itself or use a contract maker.

Two outside factors will shape the program. The first is patent timing. Semaglutide rights are expiring at different dates in different countries, and the date that applies to tablets in each market will decide where a rival oral product could launch first. Our patent and trade desk tracks those dates as they move. The second is supply. Generic semaglutide makers have already found that scaling peptide synthesis is hard, and an oral product would multiply the volume needed per patient. The Daewon oral semaglutide project will need a reliable source of high purity peptide long before it needs a sales plan, and the company has not yet said where that will come from.

Conclusion

Daewon oral semaglutide data show higher exposure than Rybelsus in two studies of 18 and 19 people, up to 3.14 times by the company's account. The results are unpublished and measure blood levels only. The supply angle is clear: Rybelsus absorbs under 1 percent of its peptide, so any carrier that lifts that figure could lower the drug substance needed per patient. Whether it does depends on a Phase 1 trial planned for 2027, an undisclosed tablet strength, and a peptide supplier Daewon has not named.