Rani's oral RT-114 tops matched injected dose, no drug-related AEs in Phase 1a
A 30-person healthy-volunteer cohort shows Rani Therapeutics' RaniPill-delivered GLP-1/2 agonist clearing subcutaneous exposure, positioning a repeat-dose obesity study for 2026.
Executive Summary
- Rani Therapeutics showed its oral capsule can deliver a GLP-1/GLP-2 dual agonist at exposure levels above a matched injected dose, with a side-effect profile consistent with the drug class rather than the delivery method.
- The registered goal of this cohort was safety and tolerability in healthy volunteers, not a metabolic or weight outcome, so the finding supports feasibility of oral delivery rather than clinical benefit.
- The company is adding a dosing cohort to refine the oral-to-injected exposure relationship before moving into a repeat-dose study in patients with obesity, the setting where the platform's clinical case will actually be tested.
- No peer program using an ingestible capsule to deliver an injectable biologic surfaced in the competitive scan, leaving this result without a direct precedent to benchmark against in this modality.
The readout
Rani Therapeutics disclosed initial results from the single-dose portion of its Phase 1 study of RT-114, an oral RaniPill capsule delivering PG-102, a GLP-1/GLP-2 dual agonist licensed from ProGen Co., Ltd. In the randomized, open-label cohort, 30 healthy volunteers received an identical 12 mg dose of PG-102 either orally through the capsule or by subcutaneous injection. Oral RT-114 achieved systemic exposure greater than 150% of the matched injected dose, with elimination half-life similar between arms at 5.6 days orally versus 5.3 days subcutaneously. No serious adverse events occurred in either arm, and no adverse events were attributed to the capsule itself; treatment-related events, including nausea, vomiting and diarrhea, were mild and transient, consistent with the known GLP-1/GLP-2 class profile. RaniRani Therapeutics Announces Positive Initial Phase 1a Data for RT-114 for the Treatment of ...Jul 15, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the endpoint measured
The trial's registered primary endpoint was safety and tolerability, assessed through treatment-emergent adverse events, not a metabolic or efficacy measure. Pharmacokinetic and pharmacodynamic comparisons between oral and subcutaneous delivery are secondary endpoints, seven of them registered alongside the single primary measure. That structure makes the bioavailability figure the headline finding, but it is a delivery-feasibility result rather than a clinical outcome: the study was designed to answer whether the capsule can get the drug into circulation safely, not whether it changes weight or glucose control. NCT06891287An Early Phase Study of RT-114 (RaniPill Containing PG-102, a GLP-1/2 Dual Agonist) in Healthy Volunteers.NCT06891287
The next step
Rani is expanding the Phase 1a study with an additional cohort of 15 healthy volunteers, each receiving two separate 12 mg doses of PG-102 through the RaniPill for a 24 mg total dose, to define the oral-to-subcutaneous pharmacokinetic relationship ahead of dose selection. The company plans to move into a Phase 1b study assessing eight weeks of repeat dosing with RT-114 in patients with obesity, expected to begin in 2026 with data anticipated in 2027. That repeat-dose, patient-population study is where the platform's exposure advantage will be tested against a clinical backdrop rather than a single-dose comparison in healthy volunteers. RaniRani Therapeutics Announces Positive Initial Phase 1a Data for RT-114 for the Treatment of ...Jul 15, 2026
Trial mechanics
NCT06891287 is a Phase 1 trial run in Australia, recruiting toward an anticipated enrollment of 60 participants, with a primary completion date that moved from March 1, 2026 to December 1, 2026 as the trial's status shifted from Not yet recruiting to Recruiting in April 2026. The enrollment target has not changed since the trial's registration, and the shift in completion timing accompanied the status change rather than a change in trial scope. No competitive trial using an oral capsule to deliver an injectable GLP-1/GLP-2 agonist was identified, leaving this program without a direct same-modality comparator in the current competitive scan. NCT06891287An Early Phase Study of RT-114 (RaniPill Containing PG-102, a GLP-1/2 Dual Agonist) in Healthy Volunteers.NCT06891287
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.