Rani Therapeutics Holdings, Inc. · NASDAQ:RANI
Rani Therapeutics — Technical Presentation (December 2022)
30 slides from Rani Therapeutics's technical presentation, December 2022
Slide 1: RT-102 Phase I Study Part 2: Repeat-Dose Update
RT-102 Phase I Study Part 2: Repeat-Dose Update December 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation and the accompanying oral statements contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act. Fo
Slide 3: Presentation Overview
Presentation Overview • Topline results from Part 2 of our RT-102 Phase 1 study – Seven-day repeat-dose study in healthy volunteers • First repeat-dose study of RaniPill capsule in humans collecting data on: – Safety – Tolerability – Device Reliability • Important data – For the RT-102 program and P
Slide 4: RT-102 Phase 1 Study Design
RT-102 Phase 1 Study Design Objective: To Evaluate the Safety, Tolerability and Pharmacokinetics of Parathyroid Hormone (1-34) (PTH) Administered Orally via RaniPill™ Capsule Part 1 : Single ascending doses of RT-102 • RT-102 Group 1: 20µg (N=15) • RT-102 Group 2: 80µg (N=15) • Control Group: Forteo
Slide 5: Part 1 Summary
Part 1 Summary • Safety & Tolerability – Both doses of RT-102 were well tolerated – No serious adverse events (SAEs) reported in the study – No adverse events (AEs) related to RaniPill reported • Device Performance – Drug delivery success rate of 95% • Pharmacokinetics – Bioavailability of PTH deliv
Slide 6: Part 2: Arvinder Dhalla, PhD, Vice President, Clinical Development
Part 2: Arvinder Dhalla, PhD Vice President, Clinical Development
Slide 7: Part 2 Study Overview
Part 2 Study Overview A Phase I Study to Evaluate the Pharmacokinetics of Parathyroid Hormone (1-34) (PTH) Administered Orally via RaniPill™ Capsule Objective To evaluate the safety and tolerability of repeat-doses of RT-102 Study Population Healthy women and Post-menopausal women (N=10) Study Site
Slide 8: Repeat-Dose: Study Procedures
Repeat-Dose: Study Procedures Days 1-6 Participant Dosed 3 hr. 6 hr. 9 hr. Fast >8 hrs. Food provided Fluoro image taken Blood Blood Blood Blood sample Sample Sample Sample Day 7 Participant Dosed 3 hr. Fast >8 hrs. Serial fluoroscopic imaging done to determine T=0 Start PK sampling….. Blood Liquids
Slide 9: Topline Results
Topline Results
Slide 10: Study Demographics
Study Demographics Healthy Women Post-Menopausal N=5 N=5 Age 25.6 years (22 - 35) 60 years (54 - 65) Race % (n/N) % (n/N) Hispanic 20 (1/5) 0 (0/5) White-non-hispanic 20 (1/5) 100 (5/5) Asian 40 (2/5) 0 (0/5) Asian-Pacific Islander 20 (1/5) 0 (0/5) Mean ± SD (Min - Max) Mean ± SD (Min - Max) Weight
Slide 11: Exclusions after Enrollment
Exclusions after Enrollment • Enrollment was done on a rolling basis to complete ten subjects, total number of participants enrolled were 17 • Seven participants did not complete 7 days of dosing due to exclusions per protocol – Two participants started menstruation on Day 4 – One participant had ca
Slide 12: Adverse Events
Adverse Events Adverse Event Incidence Constipation* 1 (10%) PTH-related Diarrhea* 1 (10%) RaniPill-related Abdominal Pain 1 (10%) * Same subject reported both AEs on different days 12
Slide 13: Daily Drug Delivery by RaniPill with Repeat-Dosing
Daily Drug Delivery by RaniPill with Repeat-Dosing Drug signal detected in 63 out of 69 deployments* = at least 91% Success Rate Subject # Type Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 1 HW ✓ ✓ ✓ ✓ ✓ ✓ ✓ 2 HW ✓ ✓ ✓ ✓ ✓ ✓ ✓ 3 HW ✓ ✓ ✓ 80% ✓ ✓ ✓ 4 HW ✓ ✓ ✓ ✓ ✓ ✓ 5 HW ✓ ✓ ✓ ✓ ✓ ✓ 6 PM ✓ ✓ ✓ ✓ ✓
Slide 14: Presence of Food Did Not Impact Device Performance
Presence of Food Did Not Impact Device Performance • On Days 1-6, food was consumed at 3 hrs. after capsule administration to all enrolled subjects • During this period, there were a total of 72 successful deployments • 35 were recorded before food was consumed (fasted) • 37 were recorded after food
Slide 15: Serum hPTH Concentration: PK Profile of PTH Delivered via RaniPill
PK Profile of PTH Delivered via RaniPill Drug levels were observed in all 10 subjects on Day 7 = 100% success rate 300 Serum hPTH Concentration RT-102 20μg Part 2 (N=10) Forteo SC 20μg Part 1 (N=10) 200 (pg/mL) 100 0 0 120 240 360 480 600 720 840 960 Time (min) • These data corroborate the high bioa
Slide 16: Repeat Doses of RT-102 Key Takeaways
Repeat Doses of RT-102 Key Takeaways • RT-102 was well tolerated with repeat dosing • No SAEs were reported in the study • Device remnants were eliminated without sequelae in all subjects • RT-102 RaniPill delivered PTH with reliability of >90% • Device performance was unaffected by presence of food
Slide 17: Next Steps Talat Imran, CEO
| ; Next Steps ™ Talat Imran, CEO . Rani THERAPEUTICS
Slide 18: Next Steps and Upcoming Potential Milestones
Next Steps and Upcoming Potential Milestones • Pre-IND meeting request • Conduct 28-day GLP study – Early 2023 • Initiate Phase 2 Study – 2H 2023 • Plan to publish RT-102 Phase 1 Study results • Additional 2023 prospective milestones: – Initiation of a Phase 1 study of RT-111 containing an ustekinum
Slide 19: Appendix
Appendix
Slide 20: Study Demographics
Study Demographics Total Cohort (N=17) Completed Dosing (N=10) Healthy Women Post-menopausal Healthy Women Post-menopausal N=11 N=6 N=5 N=5 Age 28 years (22 - 49) 58.8 years (53 - 65) 25.6 years (22 - 35) 60 years (54 - 65) Race % (n/N) % (n/N) % (n/N) % (n/N) Hispanic 18.2 (2/11) 0 (0/6) 20 (1/5) 0
Slide 21: Adverse Events
Adverse Events All Enrolled Participants Adverse Event Participants Completed 7 days (N=17) (N=10) Constipation* 1 (5.9%) 1 (10%) PTH-related Diarrhea* 1 (5.9%) 1 (10%) Headache 1 (5.9%) 0 Abdominal Pain 2 (11.8%) 1 (10%) RaniPill-related Burping 1 (5.9%) 0 Data from Part 2 of the Phase 1 study of R
Slide 22: Device Performance with Repeat Doses
Device Performance with Repeat Doses Data from 10 participants who completed the 7-day repeat-dosing Drug signal detected in 63 out of 69 deployments* At least 91% Success Rate Data from all 17 participants Drug signal detected in 82 out of 93 deployments* At least 88% Success Rate *Deployment confi
Slide 23: RT-102 Phase 1: Oral Administration of PTH (1-34) Via the RaniPill and PD Studies for Osteoporosis
RT-102 Phase 1: Oral Administration of PTH (1-34) Via the RaniPill and PD Studies for Osteoporosis
Slide 24: RT-102 Phase 1 Study Overview
RT-102 Phase 1 Study Overview Study Design To evaluate the safety, tolerability and pharmacokinetics (PK) of Parathyroid Hormone (1-34) (PTH) administered orally via the RaniPill Capsule in single ascending doses* Study Details Methods • Two RT-102 treatment groups in healthy • Transit of RaniPill c
Slide 25: RT-102 Phase 1 (Part 1) Study Results
RT-102 Phase 1 (Part 1) Study Results Study Results • RT-102 was generally well-tolerated by all subjects • No serious adverse events noted in the study • No subject excluded due to difficulty swallowing the capsule • Capsule remnants passed out in all subjects Incidence of Adverse Events RT-102 20µ
Slide 26: RaniPill Delivered PTH with Higher Bioavailability than SC
RaniPill Delivered PTH with Higher Bioavailability than SC 1000 PK Parameters RT-102-20 (N=12) 800 RT-102-80 (N=14) Forteo SC RT-102 RT-102 Forteo SC-20 (N=10) 20µg 20µg 80µg 600 Cmax (pg/mL) 128 ± 20 98 ± 10 971 ± 223 PTH (pg/ml) 400 Tmax (minutes) 13 68 60 200 AUC (pg*h/mL) 126 ± 64 342 ± 36 2600
Slide 27: RT-102 80µg PK Profile is Similar to Tymlos at 80µg
RT-102 80µg PK Profile is Similar to Tymlos®* at 80µg** RT-102 Phase I Data - Dose 80µg Tymlos Package Insert - Dose 80µg 1000 PTH Concentration 800 600 (pg/ml) 400 200 0 0 5 10 15 20 25 Time (Hours) • Cmax 971 (223) pg/mL • Cmax 812 (118) pg/mL • AUC0-24 2600 (649) pg·hr/mL • AUC0-24 1622 (641) pg·
Slide 28: RT-102 DS is Osteoanabolic in a Rat Model of Osteoporosis
RT-102 DS* is Osteoanabolic in a Rat Model of Osteoporosis Study Objective To evaluate the effect of daily dosing with RT-102 drug substance (*DS; teriparatide in Rani formulation) on bone mineral density (BMD) in an ovariectomized (OVX) rat model of osteoporosis Model & Study Design Key Endpoint Mo
Slide 29: Device Performance: Progression of Drug Delivery Success Rate
Device Performance: Progression of Drug Delivery Success Rate 100 90 Success Rate (%) 80 Highest success rate for Novo 70 Nordisk’s oral semaglutide in 60 Phase 1 study was 67%* 50 40 30 20 10 25% 50% 80% 75% 95% 0 A B C C D (N=12) (N=20) (N=20) (N=8) (N=21) Octreotide Phase I study RT-102 Phase I s
Slide 30: Phase I (Part 1) Study Summary
Phase I (Part 1) Study Summary 0 95% >300% RaniPill platform Adverse events related to RT-102 bioavailability drug delivery the RaniPill platform compared to SC injection success rate* * Success rate of Version D of the RaniPill in the per protocol population. 30
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