Rani Therapeutics Unveils New Data Supporting Transenteric GLP-1 Delivery

Rani Therapeutics Holdings, Inc., a clinical-stage biotherapeutics company, has announced new pharmacokinetic data from a preclinical study evaluating the transenteric delivery of an incretin triagonist that targets GLP-1, GIP, and glucagon receptors. This study was designed to mimic the RaniPill route of administration, a novel platform developed by Rani for the oral delivery of biologics and drugs, which promises to be an alternative to traditional subcutaneous injections.

The recent preclinical study aimed to compare the pharmacokinetic and pharmacodynamic profiles of the incretin triagonist when administered via an endoscope-guided transenteric route with those of the traditional subcutaneous injection route. Conducted in canines, the study involved two groups: one receiving the triagonist transenterically and the other receiving it via subcutaneous injection. The administered dose for both routes was 0.12 mg/kg. The study monitored blood samples over two weeks to analyze serum drug concentrations and various pharmacodynamic and safety biomarkers.

The findings revealed that a single dose of the incretin triagonist led to significant weight loss and a reduction in serum lipids, regardless of the delivery route. The weight loss observed was more pronounced with the transenteric delivery (9.7 ± 2.5 %) compared to subcutaneous injection (6.9 ± 2.1 %). The bioavailability of the drug delivered transenterically was found to be comparable to that of the subcutaneous route at the same dose. Additionally, the drug was well tolerated in both groups, with no serious adverse events or changes in safety markers reported.

Specifically, the transenteric delivery via the RaniPill achieved 80% relative bioavailability compared to the subcutaneous route, and the differences between pharmacokinetic parameters such as AUC, Cmax, and Tmax were not statistically significant. The AUC for the transenteric route was 26963.3 ± 5520.0 nmol*h/L compared to 33509.5 ± 1576.1 nmol*h/L for the subcutaneous route. The Cmax values were 334.3 ± 32.8 nmol/L for transenteric delivery versus 311.5 ± 26.1 nmol/L for subcutaneous injection, and Tmax was 16.7 ± 10.4 hours for transenteric delivery compared to 24 ± 0.0 hours for subcutaneous injection.

The pharmacokinetic data, in conjunction with previously announced pharmacodynamic data, underscore the potential of the RaniPill as a novel platform for delivering incretin triagonists orally. This development could be significant for the treatment of obesity, providing a less invasive alternative to injections with flexible dosing options.

Talat Imran, Chief Executive Officer of Rani Therapeutics, highlighted the promising nature of these preclinical results, which validate the scientific potential of the RaniPill platform. He emphasized the company's focus on advancing to a Phase 1 clinical trial for RT-114, a RaniPill capsule containing a GLP-1/GLP-2 dual-agonist for obesity treatment, expected to begin in 2025. Additionally, the company is exploring options to progress with other molecules in the obesity treatment space.

Rani Therapeutics continues to innovate in the realm of oral biologics, and the RaniPill platform could represent a breakthrough in drug delivery technology, potentially replacing the need for painful injections with convenient oral alternatives. This progress holds promise for enhancing patient compliance and expanding treatment options in the obesity sector.