Rani Therapeutics : 2024 DDW Oral Ustekinumab

AN ORALLY ADMINISTERED ROBOTIC PILL

(RP) RELIABLY AND SAFELY DELIVERS AN

USTEKINUMAB BIOSIMILAR WITH HIGH

BIOAVAILABILITY RELATIVE TO

SUBCUTANEOUS (SC) USTEKINUMAB IN

HEALTHY HUMAN SUBJECTS

Jacques Van Dam, MD, PhD

Vice President, Medical Affairs	Professor of Medicine
Rani Therapeutics, Inc.	Keck School of Medicine
San Jose, CA	University of Southern California

Joshua Myers, Son Nguyen, Nidhi Patel, April Toledo Vo, Alyson Yamaguchi, Kyle Horlen, Baber Syed, Mir Imran, Mir A. Hashim, Arvinder K. Dhalla.

Rani Therapeutics, Inc. San Jose, CA

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DISCLOSURE INFORMATION

Jacques Van Dam, MD, PhD

I disclose the following financial relationship(s) with a commercial interest

• Rani Therapeutics, Inc. San Jose, CA

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INTRODUCTION

• Purpose
• • To evaluate the pharmacokinetics (PK) of an ustekinumab biosimilar, administered via a robotic pill (RP) capsule to healthy volunteers.
• Ustekinumab
• • A monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23 and has been approved for the treatment of psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis.
  • Ustekinumab (Stelara®) has been in clinical use for over a decade. Its typical dosing regimens are 45mg or 90mg administered via SC injection every 12 weeks.

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INTRODUCTION: DRUG DELIVERY

• Route of Administration
• • Like all biologics, biosimilars, peptides, GLP-1, ustekinumab cannot be taken orally due to inactivation in the gastrointestinal tract. Ustekinumab is therefore delivered parenterally via subcutaneous (SC) injection.
• Dosing Frequency
• • Ustekinumab requires long-term injections that present a burden for patients, interfering with their quality of life and therapeutic compliance.
  • Patients overwhelmingly prefer oral dosing to injections. An effective oral alternative could improve patient compliance and encourage earlier adoption of proven therapies.

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PK SIMULATIONS OF USTEKINUMAB (45 MG SC QUARTERLY)

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	5	Stelara Current Dosing Regimen
(µg/ml)
4
Concentration
3
	2
	1
	0	0 9 18 27 37 46 55 64 73 82 91 100 110 119 128 137 146 155 164 174 183 192 201 210 219 228 237 247 256 265 274 283 292 301 311 320 329 338 347 356

Days

Current dosing regimen of 45 mg every 12 weeks results in serum concentration below therapeutic levels around week 10-11

Target Therapeutic Concentration = 0.7 µg/ml

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PK SIMULATIONS OF USTEKINUMAB

(45 MG SC QUARTERLY VS. RP 0.5 AND 0.75 MG ORAL DAILY)

	6	Stelara Current Dosing Regimen
	5	0.50mg Daily Dosing
(µg/ml)	4	0.75mg Daily Dosing
Concentration	3
	2
	1
	0
	0 9	18 26 35 44 53 61 70 79 88 96 105 114 123 132 140 149 158 167 175 184 193 202 210 219 228 237 246 254 263 272 281 289 298 307 316 324 333 342 351 360

Days

Daily dosing of 0.50 mg (red) or

0.75 mg (green) of ustekinumab in RP may maintain steady state

serum concentrations more

effectively than 45 mg every 12

weeks (blue)

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ROBOTIC PILL TECHNOLOGY

	Coating dissolves in	Needle and drug payload
000 33mm x 11mm	intestinal pH, moisture enters
dissolve, taken up by
the RP and triggers chemical
	surrounding vasculature
	reaction generating CO2

RP containing	Enteric coating protects
ustekinumab	Balloon inflates, needle is
biosimilar	RP against gastric pH	inserted through the intestinal
		wall, and payload is injected

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PHASE 1 CLINICAL TRIAL:

STUDY OVERVIEW

An Open Label, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of an Ustekinumab Biosimilar (CT-P43; Celltrion, Inc.) - Administered Orally via Robotic Pill to Healthy Volunteers

Objective	To assess safety, tolerability and PK of ustekinumab delivered orally via a
robotic pill
Study Population	Healthy men and women volunteers recruited from the general population
Study Site	Single center
End Points	PK parameters, safety and tolerability

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STUDY DESIGN

• Study Groups
• • Control Group: 0.50mg ustekinumab (Stelara) SC (N=15)
  • Group 1: 0.50mg ustekinumab biosimilar (CT-P43) in RP (N=20)
  • Group 2: 0.75mg ustekinumab biosimilar (CT-P43) in RP (N=20)
• Participants were given a single dose of the study drug (SC or PO) after an overnight fast
• Blood samples were collected at various time points over 60 days and analyzed for

ustekinumab concentrations

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STUDY DEMOGRAPHICS

	SC (0.50 mg)		Group 1	(0.50 mg)	Group 2 (0.75 mg)
N	15	20		20
Mean Age, years (Range)	29.3 (19 - 49)		28.3 (20 - 39)	30 (20 - 58)
Race
Hispanic	0% (0/15)		25%	(5/20)	5%	(1/20)
White-non-Hispanic	60% (9/15)		35%	(7/20)	75%	(15/20)
Asian	40% (6/15)		35%	(7/20)	20% (4/20)
Russian	0% (0/15)		5% (1/20)	0%	(0/20)
Body Mass Index (kg/m2)	23.8 ± 3.4		25.5 ± 3.7	22.9 ± 2.2
(Mean ± SD)

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