FRI415 Patient Preference And Proof-of-concept For A Once-daily Follicle Stimulating Hormone (FSH) Biosimilar Delivered Via An Orally Ingestible Robotic Pill (RT-112)
Authors: Yamaguchi Alyson , Horlen Kyle , Patel Nidhi , Tran Vinh , Vo April T , Medida Ramya Lekha , Myers Joshua T , Fung Leonard C , Kaminskaya Kristina , Mohan Deepa , Nguyen Vy , Nguyen Son , Syed Baber , Dhalla Arvinder K , Imran Mir , Hashim Mir A 
Published: October 2023

Disclosure: A. Yamaguchi: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. K. Horlen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. N. Patel: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. V. Tran: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A.T. Vo: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. R. Medida: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. J.T. Myers: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. L.C. Fung: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. K. Kaminskaya: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. D. Mohan: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. V. Nguyen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. S. Nguyen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. B. Syed: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A.K. Dhalla: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M. Imran: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M.A. Hashim: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics.

Background: Biotherapeutics offer effective treatments for reproductive disorders, but require painful parenteral (e.g., subcutaneous (SC)) injections, representing a burden for patients which interferes with comfort and quality of life. We have developed an orally ingestible robotic pill (RP) that can deliver biotherapeutic agents with bioavailability rivalling or surpassing that of parenteral injections. Here, we provide 1) clinical evidence of patient preference for the daily oral RP over parenteral injection therapy and 2) data from a study of awake canines demonstrating comparable serum exposures of FSH via the oral RP versus SC injection. Methods:Patient Preference Study: A total of 150 participants currently using parenteral injections were enrolled and given a mock-RP having the same physical characteristics of a RP but without a needle or drug inside. After swallowing the mock-RP, participants were asked to complete a questionnaire evaluating their experience and their preference for a pill vs. parenteral injection. Nonclinical Proof-of-Concept: Single doses of RT-112 (150 IU (n=7) and 450 IU (n=8)) were orally administered to awake, fasted Beagle dogs (7.0-13.0 kg body weight); a control group (n=3) received a dose of 20 IU/kg (∼180 IU) FSH via SC injection. Serial blood samples were collected over 5 days and serum FSH concentrations were quantified via a qualified ELISA. Results: All participants (150/150) in the patient preference study were able to swallow the mock-RP without any adverse events. Based on the questionnaire, the overall preference for an oral pill over parenteral injection was 91%, irrespective of age (21-50, 51-65, 66-75 years). Oral administration of FSH at the 2 doses via RT-112 to awake canines elicited dose proportional increases in serum drug concentrations. AUC0-t values for the 150 IU and 450 IU dose groups were 2101 ± 185 and 8179 ± 733 mIU*hr/mL, and Cmax values were 65 ± 13 and 224 ± 24 mIU/mL, respectively. The pharmacokinetic (PK) profile of the lower RT-112 dose was similar to that of the SC Control dose (AUC0-t: 2131 ± 67 mIU*hr/mL, Cmax: 52 ± 1 mIU/mL), with a relative bioavailability nearly identical (99%) to that of the SC injection. Conclusions: Patients strongly prefer an oral therapeutic option over parenteral therapy. In awake canines, FSH delivered via oral RP yielded bioavailability very similar to SC injection. These data provide early proof-of-concept of the feasibility of replacing the current parenteral injections of FSH with orally ingestible capsules utilizing the RP.

Presentation: Friday, June 16, 2023