Rani Therapeutics RT-114 oral GLP-1/2 agonist tops subcutaneous exposure
Rani Therapeutics has reported initial Phase 1a data for RT-114, its orally administered RaniPill Capsule containing PG-102, a GLP-1/GLP-2 dual agonist developed in partnership with South Korea's ProGen Co., with results showing systemic exposure exceeding that of a matched subcutaneous injection.
In the single-dose, open-label study, 30 healthy volunteers received a 12 mg dose of PG-102 either via the oral RT-114 capsule or by subcutaneous injection. The oral route achieved bioavailability greater than 150% relative to the subcutaneous comparator, a result the company describes as exceeding its own expectations. Elimination half-life was broadly comparable between arms, at 5.6 days for oral RT-114 and 5.3 days for the subcutaneous dose. No serious adverse events were reported, and treatment-related side effects such as nausea, vomiting and diarrhoea were described as mild and transient, consistent with the known tolerability profile of GLP-1/GLP-2 class drugs.
Platform significance
Rani's RaniPill platform is designed to convert injectable biologics into swallowable capsules, using a mechanical delivery mechanism in the small intestine to bypass the gut's protease-rich environment that typically degrades large molecules before they can be absorbed. Achieving oral bioavailability that exceeds subcutaneous exposure is a significant result if it holds in repeat-dose studies. The field of oral biologic delivery has historically struggled to reach even 10–20% of subcutaneous exposure, and most programmes have stalled at that threshold. If the RT-114 findings are reproducible, the RaniPill platform would represent a materially differentiated approach rather than simply a convenience reformulation.
Rani is expanding the Phase 1a study with an additional cohort of 15 healthy volunteers, each receiving two separate 12 mg oral doses of PG-102 via the RaniPill (24 mg total administered dose). The dataset from this cohort is intended to refine dose selection for the planned Phase 1b study, which will assess eight weeks of repeat dosing in patients living with obesity. The Phase 1b study is expected to begin before the end of 2026, with data anticipated in 2027.
Chief executive Talat Imran said the bioavailability result may give the company "greater flexibility to explore a higher range of serum concentrations using fewer and more practical oral doses" than previously modelled, and the expanded Phase 1a cohort reflects that reassessment.
Competitive landscape
The obesity drug market is among the most intensely contested in biopharma. GLP-1 and dual GLP-1/GLP-2 agonists are attracting multi-billion dollar investment, with Novo Nordisk and Eli Lilly dominating current approved injectable options. A credible oral biologic in this space would address a well-documented patient preference gap: adherence to weekly self-injection programmes in real-world settings is substantially lower than in clinical trials. Several companies are pursuing oral small-molecule GLP-1 receptor agonists, including Novo Nordisk's semaglutide pill, but oral delivery of a peptide biologic via a novel capsule mechanism occupies a distinct niche. Rani's collaboration with ProGen, under which costs and profits are split equally and territories divided between the two partners after Phase 2 initiation, aligns incentives for a global development push if Phase 1b data support advancement.
Investors will focus on three near-term questions: whether the greater-than-150% bioavailability figure is sustained on repeat dosing in an obese population (metabolic state can alter GI physiology), whether the GI adverse-event rate remains acceptable at the higher dose levels the expanded cohort is designed to explore, and whether Phase 1b can generate pharmacodynamic weight-loss signals that de-risk the path to a Phase 2 efficacy study.