Rani Therapeutics has announced promising preclinical data demonstrating bioequivalence between its orally administered GLP-1/GLP-2 dual agonist (RT-114) and the same drug delivered via traditional subcutaneous injection. The results mark a significant advancement in the company's efforts to develop oral alternatives to injectable obesity treatments.
In the preclinical study, RT-114—which delivers ProGen's PG-102 molecule via Rani's proprietary RaniPill® capsule—achieved a relative bioavailability of 111% compared to subcutaneous administration, with both delivery methods producing comparable weight loss of approximately 6.7% in canine subjects. Notably, the oral formulation showed less variability in weight loss outcomes than the injectable version.
"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," said Talat Imran, Chief Executive Officer of Rani Therapeutics. "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."
Dual Agonist Approach May Offer Advantages
The GLP-1/GLP-2 dual agonist mechanism of RT-114 could potentially provide benefits beyond current single-target GLP-1 therapies. According to the company, PG-102's dual-action approach may induce "higher quality weight loss," potentially delivering improved body composition and nutritional health compared to existing treatments.
This potential advantage was highlighted in previously disclosed preclinical data, where PG-102 demonstrated improved body composition (fat versus lean mass loss) compared to tirzepatide and dapiglutide in a diet-induced obese mouse model.
ProGen, Rani's development partner for RT-114, recently reported preliminary results from the Phase 1C portion of its clinical study of subcutaneous PG-102. The injectable form demonstrated weight loss in obese subjects, with an average reduction of 4.8% and up to 8.7% following just five weeks of dosing. The drug showed good tolerability with no treatment discontinuations among 73 patients across the entire Phase 1 program.
RaniPill® Platform Shows Consistent Results Across Multiple Molecules
RT-114 represents the fourth incretin-based drug to be studied preclinically using Rani's oral delivery technology. In February 2025, the company announced successful preclinical data for semaglutide delivered via the RaniPill® capsule.
"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.
The RaniPill® capsule was well-tolerated in the preclinical study with no changes in drug-related safety profile compared to subcutaneous delivery. The capsule achieved a 90% delivery success rate and was safely excreted without complications in all test subjects.
Financial Position and Development Timeline
Rani Therapeutics reported $27.6 million in cash, cash equivalents, and marketable securities as of December 31, 2024, compared to $48.5 million at the end of 2023. The company expects its current financial resources to fund operations into the third quarter of 2025 without additional funding.
For the full year 2024, Rani reported a net loss of $56.6 million, compared to $67.9 million in 2023. The reduction in net loss was primarily due to lower research and development expenses, which decreased from $39.6 million in 2023 to $26.7 million in 2024, reflecting a reduction in workforce and the timing of certain preclinical and clinical studies.
The company plans to initiate a Phase 1 clinical trial of RT-114 for the treatment of obesity in mid-2025. This study will be an important milestone in Rani's collaboration with ProGen, which began in June 2024. Under their agreement, development costs, operating profits, and losses from the commercialization of RT-114 will be equally shared between the two companies.
Market Implications
The development of effective oral alternatives to injectable GLP-1 therapies could significantly expand the market for obesity treatments. Current injectable GLP-1 receptor agonists have shown remarkable clinical success but face challenges related to patient adherence due to injection requirements and extended titration schedules.
Høiland noted that 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—potentially addressing 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," Høiland added.
As Rani advances RT-114 toward clinical trials, the company continues to build evidence supporting the RaniPill® platform's potential to transform the delivery of biologics and enable oral administration of multiple obesity treatments, potentially offering patients more convenient and accessible therapeutic options in the future.
