Rani Therapeutics Holdings, Inc., a clinical-stage biotherapeutics company focused on the oral delivery of biologics and drugs, announced pharmacokinetic and pharmacodynamic data from a preclinical study evaluating RT-114, a GLP-1/GLP-2 dual agonist (PG-102). PG-102 delivered orally via the RaniPill® capsule demonstrated comparable bioavailability and weight loss to subcutaneously (SC) injected PG-102 (“SC PG-102”). PG-102 is ProGen Co., Ltd’s (“ProGen”) Fc-fusion protein conjugated GLP-1/GLP-2 dual agonist.

“We believe that RT-114 has the potential to be a first-in-class, orally administered GLP-1/GLP-2 dual agonist for the treatment of obesity, addressing a critical gap in the treatment landscape. Despite the remarkable success of GLP-1 receptor agonists, there is a pressing need for effective oral therapies with convenient dosing strategies to eliminate the need for burdensome injections. With RT-114’s extended half-life, we are targeting a convenient, oral dosing regimen for the treatment of obesity,” said Talat Imran, Chief Executive Officer of Rani Therapeutics. “Furthermore, in our preclinical study, RT-114 achieved pharmacokinetics, bioavailability, and weight loss comparable to PG-102 delivered via subcutaneous injection. We believe that PG-102’s GLP-1/GLP-2 dual agonist construct is key to its potential to induce higher quality weight loss, positioning RT-114 to potentially deliver improved body composition and nutritional health as an oral therapy. We are encouraged by the data generated to date and look forward to advancing RT-114 into a Phase 1 clinical trial this year.”

RT-114 represents the fourth incretin-based drug to be studied preclinically in the RaniPill® capsule or via the RaniPill® route of delivery. In February 2025, Rani announced preclinical data of semaglutide delivered via the RaniPill® capsule.

ProGen recently announced preliminary results of the repeat-dose portion (Phase 1C) of its Phase 1 study where SC PG-102 demonstrated weight loss in obese subjects, with an average reduction of 4.8% and up to 8.7% following five weeks of dosing (30/60/80/80/80mg). SC PG-102 demonstrated tolerability, while reaching the target dose within one month. Among 73 patients who received SC PG-102 across the entire Phase 1 program, there were no treatment discontinuations. In previously disclosed preclinical data, PG-102 demonstrated improved body composition (fat vs. lean mass loss) compared to tirzepatide and dapiglutide in a diet-induced obese mouse model. Additional data on PG-102 will be presented at the upcoming Asian Association for the Study of Diabetes (AASD) conference this week.  

“First with semaglutide and now with RT-114, Rani has demonstrated comparable pharmacokinetics and weight loss outcomes in an oral delivery at the same dose as their respective injectable counterparts. This achievement is unprecedented when compared to existing oral GLP therapies on the market and in development," said Jesper Høiland, Senior Strategic Advisor at Rani Therapeutics and former President & EVP, USA at Novo Nordisk. "Furthermore, the short titration schedule and promising tolerability profile observed with subcutaneous PG-102 in the Phase 1C study may facilitate a quicker onset of effect. This could address a significant challenge with current GLP-1 treatment options, where patients typically do not experience clinically meaningful weight loss until after 4 to 5 months of treatment. By combining these potential advantages of PG-102 with the convenience of an oral delivery, Rani has the opportunity to create a truly differentiated product profile with RT-114.”