Rani Therapeutics Announces Preclinical Data Demonstrating Successful Oral Delivery of Semaglutide via RaniPill® HC
Rani Therapeutics (RANI) announced successful preclinical data for oral delivery of semaglutide using their RaniPill® HC platform. The study demonstrated that oral semaglutide (RT-116) achieved comparable bioavailability (107%) and pharmacokinetics to subcutaneous administration.
The crossover study involved eight canines receiving 0.5mg doses, with successful delivery in 7 of 8 subjects. Both oral and subcutaneous administration groups showed similar weight loss patterns and decreases in serum triglycerides and cholesterol. The RaniPill® HC was well-tolerated with no serious adverse events.
The company aims to develop a once-weekly oral administration of semaglutide, potentially offering a more convenient alternative to current injectable treatments. Rani also announced plans to initiate a Phase 1 study for RT-114, their GLP-1/GLP-2 dual agonist for obesity treatment, in 2025.
Rani Therapeutics (RANI) ha annunciato dati preclinici di successo per la somministrazione orale di semaglutide utilizzando la loro piattaforma RaniPill® HC. Lo studio ha dimostrato che il semaglutide orale (RT-116) ha raggiunto una bioavailability comparabile (107%) e farmacocinetica simile a quella dell'amministrazione sottocutanea.
Lo studio cross-over ha coinvolto otto cani che ricevevano dosi di 0,5 mg, con una somministrazione riuscita in 7 su 8 soggetti. Sia il gruppo di somministrazione orale che quello sottocutanea hanno mostrato schemi di perdita di peso simili e riduzioni nei trigliceridi e colesterolo sierici. Il RaniPill® HC è stato ben tollerato, senza eventi avversi gravi.
La società mira a sviluppare una somministrazione orale settimanale di semaglutide, potenzialmente offrendo un'alternativa più comoda ai trattamenti attuali iniettabili. Rani ha anche annunciato piani per avviare uno studio di Fase 1 per RT-114, il loro dual agonista GLP-1/GLP-2 per il trattamento dell'obesità, nel 2025.
Rani Therapeutics (RANI) anunció datos preclínicos exitosos para la administración oral de semaglutida utilizando su plataforma RaniPill® HC. El estudio demostró que la semaglutida oral (RT-116) alcanzó una bioactividad comparable (107%) y farmacocinética similar a la administración subcutánea.
El estudio cruzado involucró a ocho caninos que recibieron dosis de 0.5 mg, con una administración exitosa en 7 de 8 sujetos. Tanto los grupos de administración oral como subcutánea mostraron patrones de pérdida de peso similares y reducciones en los triglicéridos y colesterol en suero. El RaniPill® HC fue bien tolerado sin eventos adversos graves.
La compañía tiene como objetivo desarrollar una administración oral semanal de semaglutida, ofreciendo potencialmente una alternativa más conveniente a los tratamientos inyectables actuales. Rani también anunció planes para iniciar un estudio de Fase 1 para RT-114, su agonista dual de GLP-1/GLP-2 para el tratamiento de la obesidad, en 2025.
라니 테라퓨틱스 (RANI)는 RaniPill® HC 플랫폼을 사용하여 세마글루타이드의 경구 전달에 대한 성공적인 전임상 데이터를 발표했습니다. 연구 결과 경구 세마글루타이드 (RT-116)가 비교 가능한 생체이용률 (107%)과 약리학적 동태를 나타냈습니다.
교차 연구에는 0.5mg 용량을 투여받은 8마리의 개가 포함되었으며, 8마리 중 7마리에서 성공적인 전달이 이루어졌습니다. 경구 및 피하 투여 그룹 모두 유사한 체중 감소 패턴과 혈청 중성지방 및 콜레스테롤의 감소를 보였습니다. RaniPill® HC는 심각한 부작용 없이 잘 견딜 수 있었습니다.
회사는 세마글루타이드의 주간 경구 투여를 개발할 계획이며, 현재의 주사 치료에 비해 더 편리한 대안을 제공할 수 있을 것으로 기대하고 있습니다. Rani는 또한 2025년에 비만 치료를 위한 GLP-1/GLP-2 이중 작용제인 RT-114에 대한 1상 연구를 시작할 계획을 발표했습니다.
Rani Therapeutics (RANI) a annoncé des données précliniques réussies pour l'administration orale de sémaglutide en utilisant leur plateforme RaniPill® HC. L'étude a démontré que le sémaglutide oral (RT-116) a atteint une biodisponibilité comparable (107%) et une pharmacocinétique similaire à celle de l'administration sous-cutanée.
Cette étude croisée a impliqué huit chiens recevant des doses de 0,5 mg, avec une administration réussie chez 7 des 8 sujets. Les groupes d'administration orale et sous-cutanée ont montré des schémas de perte de poids similaires et des baisses des triglycérides et du cholestérol sériques. Le RaniPill® HC a été bien toléré, sans événements indésirables graves.
La société vise à développer une administration orale hebdomadaire de sémaglutide, offrant potentiellement une alternative plus pratique aux traitements injectables actuels. Rani a également annoncé des plans pour initier une étude de Phase 1 pour RT-114, leur agoniste dual GLP-1/GLP-2 pour le traitement de l'obésité, en 2025.
Rani Therapeutics (RANI) hat erfolgreiche präklinische Daten zur oralen Verabreichung von Semaglutid über ihre RaniPill® HC-Plattform veröffentlicht. Die Studie zeigte, dass orales Semaglutid (RT-116) eine vergleichbare Bioverfügbarkeit (107%) und Pharmakokinetik im Vergleich zur subkutanen Verabreichung erreichte.
Die Kreuzungsstudie umfasste acht Hunde, die eine Dosis von 0,5 mg erhielten, wobei bei 7 von 8 Probanden eine erfolgreiche Verabreichung stattfand. Sowohl die Gruppen für orale als auch subkutane Verabreichung zeigten ähnliche Muster bei der Gewichtsreduktion sowie Rückgänge bei Serumtriglyceriden und Cholesterin. Der RaniPill® HC wurde gut vertragen, ohne schwerwiegende Nebenwirkungen.
Das Unternehmen hat sich zum Ziel gesetzt, eine wöchentliche orale Verabreichung von Semaglutid zu entwickeln, die potenziell eine bequemere Alternative zu den derzeitigen injizierbaren Behandlungen darstellt. Rani gab auch Pläne bekannt, eine Phase-1-Studie für RT-114, ihren GLP-1/GLP-2-Dualagonisten zur Behandlung von Fettleibigkeit, im Jahr 2025 zu initiieren.
- Successful preclinical results showing 107% bioavailability compared to subcutaneous administration
- Comparable pharmacokinetics and weight loss effects to injectable version
- High delivery success rate (7 of 8 subjects) with no serious adverse events
- Targeting the $3.1B semaglutide market (WEGOVY® first half 2024 sales)
- Still in preclinical stage, requiring extensive clinical trials before potential commercialization
- One failed delivery out of eight subjects in the study
Insights
The preclinical results for Rani's oral semaglutide delivery system represent a potentially significant advancement in the $3.1 billion GLP-1 obesity market. The data reveals three critical technical achievements:
- Exceptional bioavailability of 107% compared to subcutaneous injection - notably superior to traditional oral peptide delivery systems which typically achieve only single-digit bioavailability
- Matching pharmacokinetic profiles (Cmax, Tmax, AUC) between oral and injectable delivery, suggesting reliable drug absorption
- Comparable weight loss outcomes and metabolic benefits, indicating preserved therapeutic efficacy
The RaniPill® HC platform appears to solve key challenges that have oral GLP-1 delivery to date. Unlike RYBELSUS®, which requires daily dosing and higher drug quantities to overcome poor absorption, RaniPill® achieves injection-like delivery with weekly dosing. This could provide significant competitive advantages in patient convenience and adherence.
While these preclinical results are promising, several important questions remain for clinical development: 1) Will human pharmacokinetics match the canine data? 2) Can manufacturing be scaled cost-effectively? 3) Will the oral delivery system maintain consistency across patient populations?
The upcoming Phase 1 trial of RT-114 (GLP-1/GLP-2 dual agonist) will be particularly important as it represents Rani's first clinical validation in the obesity space. Success could position Rani as a key player in next-generation oral GLP-1 delivery technology.
- Oral semaglutide administered via the RaniPill® HC (RT-116) demonstrated comparable bioavailability, pharmacokinetics and weight loss to subcutaneous administration -
- RT-116 was well tolerated with no serious adverse events -
- Data adds to growing body of evidence of the RaniPill® platform’s potential to enable oral delivery of multiple obesity treatments -
- Phase 1 study for RT-114, an oral GLP-1/GLP-2 dual agonist for the treatment of obesity, expected to initiate in 2025 -
SAN JOSE, Calif., Feb. 05, 2025 (GLOBE NEWSWIRE) -- Rani Therapeutics Holdings, Inc. (“Rani Therapeutics” or “Rani”) (Nasdaq: RANI), a clinical-stage biotherapeutics company focused on the oral delivery of biologics and drugs, today announced new pharmacokinetic and pharmacodynamic data from a preclinical study evaluating the oral delivery of the glucagon-like peptide-1 receptor (GLP-1) agonist semaglutide administered via the RaniPill® capsule.
Semaglutide is a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor mimicking its activity. GLP-1 is an incretin hormone and enterogastrone that stimulates insulin secretion, inhibits glucagon secretion, delays gastric emptying and reduces the production of stomach acid serving as a physiological regulator of appetite and food intake.
“We believe these data provide further validation of the RaniPill® oral delivery platform across a wide variety of injectable obesity treatments. We are encouraged to see that delivery of semaglutide via the RaniPill® capsule demonstrated comparable bioavailability, pharmacokinetics and weight loss to subcutaneous administration of semaglutide at the same dose,” said Talat Imran, Chief Executive Officer of Rani Therapeutics. “The target product profile of semaglutide in the RaniPill® capsule would be once-weekly oral administration of semaglutide therapy, which we believe may be more convenient for patients and could lead to improved adherence. Overall, the totality of the preclinical data we have generated in the obesity space demonstrating the successful delivery of both single and triagonist incretin therapies gives us confidence to continue building our obesity portfolio to unlock the true value of the RaniPill® technology. Looking ahead, we are excited to begin our Phase 1 study for RT-114, Rani’s GLP-1/GLP-2 dual agonist in partnership with ProGen this year.”
Currently, semaglutide is only available as a subcutaneous injection (SC) for the treatment of obesity and is marketed in the U.S. by Novo Nordisk as WEGOVY®. Worldwide sales for WEGOVY® were approximately
“There are currently no approved orally-administered GLP-1 agonists on the market for the treatment of obesity,” said Jesper Høiland, Senior Strategic Advisor for Rani Therapeutics and former executive at Novo Nordisk. “While RYBELSUS® is an oral version of semaglutide approved to improve glycemic control in adults with type 2 diabetes mellitus, it requires daily administration at a significantly higher dose than the subcutaneous equivalent. In comparison, the RaniPill HC harnesses advanced technology to deliver the same dose as the subcutaneous injection of semaglutide with expected weekly oral administration. I believe that a convenient, once-weekly oral version of semaglutide delivered via the RaniPill HC has the potential to be transformational as a next generation treatment that would impact how obesity is treated worldwide.”
Study Design
- The nonclinical pharmacokinetic (PK) and pharmacodynamic (PD) study was conducted to examine the effects of semaglutide delivered orally via the RaniPill (RT-116) versus a subcutaneous (SC) injection comparator group.
- The 2x2 crossover study was conducted in two parts with a period of 4 weeks separating the two groups to evaluate the PK, PD and safety of RT-116.
- Eight canines were randomized into two groups who received 0.5mg of semaglutide delivered via oral administration of the RaniPill® HC (N=4) or subcutaneous injection (N=4).
- Endpoints included plasma drug concentrations, body weight, food intake, lipid profile, and safety.
Data Highlights
- Semaglutide was successfully delivered in 7 of 8 canines that received the RaniPill® capsule.
- Semaglutide administered via the RaniPill® capsule was well tolerated with no serious adverse events.
- Cmax, Tmax, and AUC were comparable for semglutide administered via RaniPill® capsule and subcutaneous administration of semaglutide.
- Oral administration via the RaniPill® capsule demonstrated bioavailability and biological activity comparable to subcutaneous administration.
- The relative bioavailability of oral semaglutide was
107% versus subcutaneous administration. - Both groups saw comparable weight loss which appeared to be driven by decreased food intake that coincided with rises in plasma drug levels thus indicating there is a PD effect to treatment.
- Both groups saw comparable moderate decreases in serum triglycerides and cholesterol.
| Route | Cmax (ng/mL) | Tmax (days) | Tlast (days) | AUClast (ng/mL*day) |
| Oral (RT-116) | 941 ± 90 | 1.3 ± 0.3 | 17 ± 2 | 3630 ± 222 |
| SC | 948 ± 120 | 1.3 ± 0.3 | 17 ± 1 | 3390 ± 402 |
| All data is mean ± standard error. | ||||
Near-Term Milestone Expectations:
- Initiation of Phase 1 clinical trial of RT-114 containing a GLP-1/GLP-2 dual agonist for the treatment of obesity expected in 2025.
About Rani Therapeutics
Rani Therapeutics is a clinical-stage biotherapeutics company focused on advancing technologies to enable the development of orally administered biologics and drugs. Rani has developed the RaniPill® capsule, which is a novel, proprietary and patented platform technology, intended to replace subcutaneous injection or intravenous infusion of biologics and drugs with oral dosing. Rani has successfully conducted several preclinical and clinical studies to evaluate safety, tolerability and bioavailability using RaniPill® capsule technology. For more information, visit ranitherapeutics.com.
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the expected initiation of a Phase 1 trial of RT-114 in 2025, the potential of the RaniPill® platform to enable oral delivery of multiple obesity treatments and validation of such potential through preclinical data, the target product profile of semaglutide delivered via the RaniPill® capsule, the novelty, convenience and attractiveness of a once-weekly oral semaglutide treatment for patients, Rani’s confidence to continue building an obesity portfolio, the potential of a once-weekly oral version of semaglutide in the RaniPill® capsule to deliver the same benefits as subcutaneous delivery and to impact patients’ lives, the sufficiency of Rani’s cash reserves, and future financial performance. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believe,” “would,” “potential,” “expect,” “continue” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Rani’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Rani’s business in general and the other risks described in Rani’s filings with the Securities and Exchange Commission, including Rani’s annual report on Form 10-K for the year ended December 31, 2023, and subsequent filings and reports by Rani. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Rani undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.
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FAQ
What were the key findings of RANI's preclinical semaglutide study in February 2024?
When will Rani Therapeutics begin Phase 1 trials for RT-114?
How does RANI's RaniPill® HC compare to existing semaglutide treatments?
What is the market opportunity for RANI's oral semaglutide delivery system?
