UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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the Securities Exchange Act of 1934
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 7.01 Regulation FD Disclosure.
On February 5, 2024, Rani Therapeutics Holdings, Inc. (the “Company” or “Rani”) issued a press release to announce topline results from the RT-111 Phase 1 clinical trial. A copy of the press release is attached hereto as Exhibit 99.1 and is incorporated herein by reference. The Company is also furnishing a copy of a presentation (the “Presentation”) that the Company intends to use, in whole or in part, during discussions with external parties. A copy of the Presentation is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated by reference herein. All of the information furnished in this Item 7.01 and Item 9.01 (including Exhibit 99.1 and Exhibit 99.2) shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (“Exchange Act”), and shall not be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.
Item 8.01 Other Events.
On February 5, 2024, Rani announced topline results from the RT-111 Phase 1 clinical trial.
Study Design
A single-center, open-label Phase 1 study of RT-111, a RaniPill capsule containing ustekinumab biosimilar, was conducted in Australia. The study evaluated the safety and tolerability of a single administration of RT-111 in healthy adult volunteers. Of the 55 participants, 20 orally ingested RT-111 containing a single 0.5mg dose of ustekinumab biosimilar and 20 orally ingested RT-111 containing a single 0.75mg dose of ustekinumab biosimilar, while a control group of 15 participants received a single 0.5mg subcutaneous (SC) injection of STELARA® (ustekinumab), a commercial formulation of ustekinumab.
Participants were fasted overnight prior to dose administration. Blood samples were collected at various time points over 60 days and analyzed for ustekinumab concentrations. Blood samples were analyzed for anti-drug antibodies at three timepoints.
Topline Results
Safety and Tolerability
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Stelara® SC 0.50 mg N=15 |
RT-111 0.50 mg N=20 |
RT-111 0.75 mg N=20 |
Drug Signal Detected |
N=15 |
N=19 |
N=16 |
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Number of ADA Positive Cases |
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Total ADA Positive* |
N |
4 |
2 |
6 |
% |
27% |
11% |
38% |
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* ADA positive post dosing, increase in titer compared to pre-dose level
Pharmacokinetics
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Stelara® SC 0.50mg |
RT-111 0.50mg |
RT-111 0.75mg |
Cmax (ng/mL) |
56 ± 4 |
67 ± 7 |
92 ± 8 |
Tmax (days) |
10 ± 0.8 |
3.1 ± 0.2* |
3.3 ± 0.2* |
AUC (day*ng/mL) |
1,566 ± 130 |
1,315 ± 150 |
1,814 ± 165 |
Bioavailability |
-- |
84% |
-- |
Data are Mean ± SE from all subjects, including those with anti-drug antibodies. *p<0.0001 significantly different from SC group.
This report contains "forward-looking" statements, including statements regarding topline results from the RT-111 Phase 1 study. Actual results may differ materially from those set forth in this report due to the risks and uncertainties inherent in research and development, including the risk that initial (or topline) clinical results do not report on all data from a clinical trial that may be important for development or regulatory approval, the risk that results from earlier clinical trials may not be indicative of future clinical results, as well as other risks detailed in the "Risk Factors" section of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022 as well as discussions of potential risks, uncertainties and other important factors in the Company’s other filings with the U.S. Securities and Exchange Commission. The Company undertakes no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
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Exhibit Description |
99.1 |
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Press Release of Rani Therapeutics Holdings, Inc. dated February 5, 2024 |
99.2 |
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104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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Rani Therapeutics Holdings, Inc. |
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Date: |
February 5, 2024 |
By: |
/s/ Svai Sanford |
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Svai Sanford Chief Financial Officer |
Exhibit 99.1
Rani Therapeutics Announces Positive Topline Results from Phase 1 Study of
an Oral Anti-Interleukin 12/23 Antibody (RT-111)
- RT-111 achieved high bioavailability in humans -
- RT-111 was well-tolerated, with no serious adverse events -
- Celltrion has right of first negotiation to acquire worldwide rights to RT-111 following a Phase 1 clinical trial that meets its primary endpoints –
- Rani has now successfully completed three Phase 1 trials using RaniPill® technology -
- Company to host conference call today at 8:30 a.m. ET / 5:30 a.m. PT –
SAN JOSE, Calif., February 5, 2024 -- 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 positive topline results from its Phase 1 clinical study of RT-111, a RaniPill® capsule containing an ustekinumab biosimilar, CT-P43. In the study, RT-111 was well-tolerated and delivered ustekinumab with high bioavailability.
“We are highly encouraged by the positive results from our Phase 1 study for RT-111 – our third successfully completed Phase 1 trial using RaniPill® technology. To our knowledge, RT-111 is the first ever oral monoclonal antibody to achieve high bioavailability in humans,” said Talat Imran, Chief Executive Officer of Rani. “These data provide clinical validation of our ability to successfully transform an injectable large molecule into an oral pill. Specifically for this program, we believe RT-111 has the potential to offer a highly differentiated dosing regimen for patients with psoriasis compared to both injectable biologics and oral small molecules and peptides. The success of the Phase 1 study of RT-111 marks another significant milestone for the Rani team, as we diligently work towards making oral biologics a reality for the millions of patients living with autoimmune conditions.”
Ustekinumab is a human IgG1қ monoclonal antibody that binds with specificity to the p40 protein subunit used by both the interleukin-12 and interleukin-23 (IL-12 and IL-23) cytokines. Currently, ustekinumab is available only as a subcutaneous injection (SC) and is marketed in the United States by Janssen as STELARA® for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, moderate to severe Crohn’s disease, and moderate to severe ulcerative colitis, all of which have large unmet medical needs for oral treatment. Sales for STELARA were approximately $6.4 billion in the United States and approximately $9.7 billion worldwide in 2022.
Rani’s single-center, open label, Phase 1 study of RT-111 was conducted in Australia. The study evaluated the safety, tolerability, and pharmacokinetics (PK) of RT-111 in healthy adult volunteers. The study enrolled 20 participants each in RT-111 0.5mg and 0.75mg dose groups, and 15 participants in a STELARA (ustekinumab) 0.5mg subcutaneous (SC) injection group.
Phase 1 Topline Results
Pharmacokinetics
Pharmacokinetics of Ustekinumab (CT-P43)
Oral (RT-111) vs SC Injection
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Stelara® SC 0.50mg |
RT-111 0.50mg |
RT-111 0.75mg |
Cmax (ng/mL) |
56 ± 4 |
67 ± 7 |
92 ± 8 |
Tmax (days) |
10 ± 0.8 |
3.1 ± 0.2* |
3.3 ± 0.2* |
AUC (day*ng/mL) |
1,566 ± 130 |
1,315 ± 150 |
1,814 ± 165 |
Data are Mean ± SE from all subjects, including those with anti-drug antibodies. *p<0.0001 significantly different from SC group.
The ustekinumab biosimilar used in RT-111 is manufactured and supplied by Celltrion, Inc. (“Celltrion”) under Rani’s License and Supply Agreement with Celltrion announced in January 2023. Under that agreement, Celltrion exclusively supplies to Rani the ustekinumab biosimilar drug substance (CT-P43) required for RT-111. Rani is granted an exclusive license to use CT-P43 in the development and commercialization of RT-111, and Celltrion is granted a right of first negotiation to acquire worldwide rights to RT-111 following a Phase 1 clinical trial that meets its primary endpoint(s).
Conference Call
Rani will host a corresponding conference call and live webcast at 8:30 a.m. ET / 5:30 a.m. PT on February 5, 2024, to discuss the results from its Phase 1 clinical trial of RT-111. Individuals interested in listening to the live conference call may do so by using the webcast link in the “Investors” section of the company’s website at www.ranitherapeutics.com. A webcast replay will be available in the investor relations section on the company’s website for 90 days following the completion of the call.
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 www.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 potential for RT-111 to be an alternative oral treatment option compared to burdensome injectables for autoimmune conditions, and the potential for Rani to make oral biologics a reality for millions of patients living with autoimmune conditions. 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 “intend” and “potential” 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, 2022, 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.
Investor Contact:
Media Contact:
Our mission at Rani is to end painful injections for the millions of patients suffering from chronic diseases. Rani Therapeutics Corporate Presentation February 2024 NASDAQ: RANI
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. Forward-looking statements are based on information available at the time those statements are made or on management's good faith beliefs and assumptions as of that time with respect to future events, and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in, or suggested by, the forward-looking statements. In light of these risks and uncertainties, the forward-looking events and circumstances discussed in this presentation and the accompanying oral statements may not occur and actual results could differ materially from those anticipated or implied in the forward-looking statements. These risks and uncertainties include Rani Therapeutics Holdings, Inc.’s (“Rani,” “we,” “us,” or “our”) future financial performance, including our expectations regarding our revenues, cost of revenues, operating expenses, and our ability to achieve and maintain future profitability, those risks inherent in the preclinical and clinical development process and the regulatory approval process, the risks and uncertainties in commercialization and gaining market acceptance, the commercial potential of oral biologics, our ability to complete development of the RaniPill® HC or any redesign and conduct additional preclinical and clinical studies of the RaniPill HC or any future design of the RaniPill to accommodate higher target payloads, the risks associated with protecting and defending our patents or other proprietary rights, the risk that our proprietary rights may be insufficient to protect our product candidates, the risk that we will be unable to obtain necessary capital when needed on acceptable terms or at all, our ability to enter into strategic partnerships and to achieve the potential benefits of such partnerships, competition from other products or procedures, our reliance on third-parties to conduct our clinical and non-clinical trials, the ability of our restructuring announced in November 2023 to deliver the expected results, our reliance on single-source third-party suppliers to manufacture clinical, non-clinical and any future commercial supplies of our product candidates, our ability to continue to scale and optimize our manufacturing processes by expanding our use of automation, our expectations regarding the period during which we qualify as an emerging growth company under the JOBS Act, our expectations regarding customer demand for our product candidates, increased regulatory requirements and other factors that are set forth in our filings with the Securities and Exchange Commission (“SEC”), including under the caption “Risk Factors” in our Annual Report on Form 10-K and our Quarterly Reports on Form 10-Q, and our other public filings made with the SEC and available at www.sec.gov. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will” or “would,” or the negative of these terms or other comparable terminology. You should not put undue reliance on any forward-looking statements. Forward-looking statements should not be read as a guarantee of future performance or results, and will not necessarily be accurate indications of the times at, or by, which such performance or results will be achieved, if at all. Except as required by law, Rani does not undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise. This presentation and the accompanying oral statements contain statistical data, estimates and forecasts that are based on independent industry publications or other publicly available information, as well as other information based on our internal sources. This information involves many assumptions and limitations, and you are cautioned not to give undue weight to such information. We have not independently verified the accuracy or completeness of the information contained in the industry publications and other publicly available information. Accordingly, we make no representations as to the accuracy or completeness of that information nor do we undertake to update such information after the date of this presentation. Trade names, trademarks and service marks of other companies appearing in this presentation are the property of their respective owners. Solely for convenience, the trademarks and trade names referred to in this presentation appear without the ® and ™ symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights, or the right of the applicable licensor to these trademarks and tradenames. Forward-Looking Statements
Mir Hashim, Ph.D. Chief Scientific Officer Talat Imran Chief Executive Officer Eric Groen General Counsel Svai Sanford Chief Financial Officer Rani Therapeutics is a public, clinical-stage biotech company developing a platform technology for the oral delivery of biologic drugs. Betsy Gutierrez Vice President, Quality Kate McKinley Chief Business Officer Arvinder Dhalla, Ph.D. Vice President, Clinical Development Jacques Van Dam, M.D. Vice President, Medical Affairs
Our mission at Rani is to end painful injections for the millions of patients suffering from chronic diseases FOCUS: TECHNOLOGY: PIPELINE: DISCOVERY: Oral Delivery of Biologic Drugs with Bioavailability Comparable to Parenteral Products GO HC 3mg Capacity Solid Drug Formulation 200 µL Capacity Liquid Drug Formulation (High Capacity) Immunology & Endocrinology Obesity, Nanobodies, Hemophilia, Bispecific MABs, Fertility 425+ Patent Applications, 225+ Granted Patents
RT-XXX refers to the RaniPill™ capsule containing a biologic in a proprietary Rani formulation * Clinical timelines are subject to potential regulatory agency review delays ** Partnered with Celltrion, Inc. Celltrion grants Rani a license and drug supply for the drug and has a right of first negotiation following a Phase 1 study INDICATION(S) FORMULATION PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 KEY MILESTONE* CORE PROGRAMS RT-111 Psoriasis Phase 1 Study Completed RT-102 Osteoporosis Initiate Phase 2 in 2024 RT-105 Psoriatic Arthritis Initiate Phase 1 RT-110 Hypo-parathyroidism Initiate Phase 1 Development Pipeline PTH-Hypo PTH-OP Adalimumab** Ustekinumab**
RT-XXX refers to the RaniPill™ capsule containing a biologic in a proprietary Rani formulation * Clinical timelines are subject to potential regulatory agency review delays ** Partnered with Celltrion, Inc. Celltrion grants Rani a license and drug supply for the drug and has a right of first negotiation following a Phase 1 study INDICATION(S) FORMULATION PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 KEY MILESTONE* CORE PROGRAMS RT-111 Psoriasis Phase 1 Study Completed RT-102 Osteoporosis Initiate Phase 2 in 2024 RT-105 Psoriatic Arthritis Initiate Phase 1 RT-110 Hypo-parathyroidism Initiate Phase 1 Development Pipeline PTH-Hypo PTH-OP Adalimumab** Ustekinumab**
RT-111 Phase 1 Study Data
Study Overview A Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of RT-111 – RaniPill Capsule Containing Ustekinumab (CT-P43) – Administered Orally to Healthy Volunteers Objective To assess safety, tolerability and PK of Ustekinumab delivered via Oral RaniPill Study Population Healthy men and women volunteers recruited from the general population Study Site Single site in Australia End Points PK parameters, safety and tolerability
Study Groups Control Group: 0.50 mg Stelara SC (N=15) RT-111 Group: 0.50 mg CT-P43 in RaniPill (N=20) RT-111 Group: 0.75 mg CT-P43 in RaniPill (N=20) Protocol Participants were given a single dose of the study drug (SC or Oral) after an overnight fast Blood samples were collected at various time points over 60 days and analyzed for ustekinumab concentrations Blood samples were analyzed for anti-drug antibodies at 3 timepoints Excretion of device remnants confirmed with imaging Study Design: Single Ascending Doses
Pharmacokinetics
PK Profiles of Oral Ustekinumab Biosimilar (RT-111) vs SC Stelara Injection Group Cmax (ng/mL) Tmax (days) AUC0-t (day.ng/mL) SC 0.5mg (N=15) 56 ± 4 10 ± 0.8 1,566 ± 130 RT-111 0.5mg (N=19) 67 ± 7 3.1 ± 0.2 1,315 ± 150 RT-111 0.75mg (N=16) 92 ± 8 3.3 ± 0.2 1,814 ± 165 Pharmacokinetic Parameters Data shown are Mean ± SE, Data pending final QA review. Estimated bioavailability based on 0.5mg dose Estimated Bioavailability Relative to SC 84%
Safety & Tolerability
Adverse Events SC, 0.50 mg (N=15) RT-111, 0.50 mg (N=20) RT-111, 0.75 mg (N=20) All 1 2 0 Drug-Related Abdominal Bloating 0 1 (5%) 0 Injection Site Rash/Reaction 1 (6.7%) 0 0 RaniPill-Related Burning Sensation in stomach* N/A 1 (5%) 0 Incidence of Adverse Events *Burning sensation in stomach perceived 1 hour after capsule administration and lasted for 30 minutes. However, drug levels were not seen for 10 hours after capsule administration indicating that the capsule had not deployed at time of the reported pain which suggests that this AE is not related to the drug or RaniPill deployment. However, presence of the undeployed capsule in the stomach could have causality to the reported pain.
Incidence of Anti-Drug Antibodies (ADAs) Stelara SC 0.50 mg N=15 RT-111 0.50 mg N=20 RT-111 0.75 mg N=20 Drug Signal Detected N=15 N=19 N=16 Number of ADA Positive Cases Total ADA Positive* N 4 2 6 % 27% 11% 38% Incidence of ADAs *ADA positive post dosing, increase in titer compared to pre-dose level N=15 N=19 N=16
Summary RT-111 was well-tolerated No SAEs Oral delivery of Ustekinumab biosimilar via RaniPill with High Bioavailability No meaningful difference in ADA development via Rani route of delivery compared to SC injection
RT-111 Oral Ustekinumab Target Product Profile
Rani - Confidential Psoriasis Competitive Landscape – Select Injectables(1) Significant Potential Opportunity to Capture Portion of Psoriasis Market Based on Improvement in Convenience and Potential Improved Efficacy Humira Cosentyx Taltz Tremfya Skyrizi Stelara Potential RaniPill Opportunity Administration SC SC SC SC SC SC Oral Maintenance Frequency Q2W Q4W Q4W Q8W Quarterly Quarterly 3-Day Monthly Short Course Target TNF-α IL-17A IL-17A IL-23 IL-23 IL-12/IL-23 IL-12/IL-23 Revenue* $21.2B $4.8B $2.5B $2.7B $5.2B $9.7B -- Total Number Annual SC Injections 26 13-26 13 6-7 4 4 0 48-60 Week % Patients PASI 75** 63% 74% 74-83% 88% 92% 89% Efficacy Similar to Injectable 12 - 16 Week % Patients PASI 75** 71-78% 75-87% 87-90% 83-91% 87-89% 66-76% Targeting 81+% 17 SC = subcutaneous * Product revenue from all indications in 2022. ** Data do not represent head-to-head studies.
Rani - Confidential Psoriasis Competitive Landscape – Select Orals(2) Significant Potential Opportunity to Capture Portion of Psoriasis Market Based on Improvement in Convenience and Potential Improved Efficacy Otezla Sotyktu JNJ-2113*** (PTG-200) Potential RaniPill Opportunity Frequency BID Daily QD / BID 3-Day Monthly Short Course Target PDE4 TYK2 IL-23 IL-12/IL-23 Revenue* $2.2B $.1B (Q1-Q3 2023) NA -- Total Number of Pills 730 365 365 / 730 36 52 Week % Patients PASI 75** 61% 72.6% NA Efficacy Similar to Injectable 12 - 16 Week % Patients PASI 75** 33% 61% 65% / 79% Targeting 81+% 18 * Product revenue from all indications in 2022. unless otherwise indicated. *** Not yet approved. ** Data do not represent head-to-head studies.
Historical Data Shows Potential Opportunity to Improve Efficacy and Safety with Higher Loading Doses Dose Groups One 45mg dose One 90mg dose Four weekly 45mg dose Four weekly 90mg dose 75 PASI Score 52% 59% 67% 81% 90 PASI Score 23% 30% 44% 52% Patients with at least 1 AE 90% 81% 78% 68% Ustekinumab Efficacy at 12 Weeks* * Data from third party study - N Engl J Med 2007; 356:580-592 DOI: 10.1056/NEJMoa062382, February 8, 2008. Safety data at 20 weeks.
Historical Data Shows Potential Opportunity to Improve Efficacy and Safety with Higher Loading Doses Dose Groups One 45mg dose One 90mg dose Four weekly 45mg dose Four weekly 90mg dose 75 PASI Score 52% 59% 67% 81% 90 PASI Score 23% 30% 44% 52% Patients with at least 1 AE 90% 81% 78% 68% Ustekinumab Efficacy at 12 Weeks* * Data from third party study - N Engl J Med 2007; 356:580-592 DOI: 10.1056/NEJMoa062382, February 8, 2008. Safety data at 20 weeks.
Historical Data Shows Potential Opportunity to Improve Efficacy and Safety with Higher Loading Doses Dose Groups One 45mg dose One 90mg dose Four weekly 45mg dose Four weekly 90mg dose 75 PASI Score 52% 59% 67% 81% 90 PASI Score 23% 30% 44% 52% Patients with at least 1 AE 90% 81% 78% 68% Ustekinumab Efficacy at 12 Weeks* * Data from third party study - N Engl J Med 2007; 356:580-592 DOI: 10.1056/NEJMoa062382, February 8, 2008. Safety data at 20 weeks.
The RaniPill Could Enable Higher Loading Phase Doses with the Convenience of Oral Administration Simulated RaniPill+Ustekinumab Loading Dose Serum Concentrations at 12 Weeks Potential to reach PASI 75 = 81% at Week 12 Daily Oral Administration with RaniPill Could Deliver Higher Loading Dose Regimen (RaniPill Dosing) Concentration (µg/ml) Days (Stelara Dosing) Potential for Better Treatment of Acute Flare Ups at the Start of Therapy Simulation based on ustekinumab published data (see Table 10 of BLA Number 125,261/ Supplement 150 of Janssen Biotech, Inc. submitted to FDA on September 30, 2019).
Current Stelara Maintenance Phase Concentration (µg/ml) Days Current maintenance dosing for Stelara is 1 injection every 12 weeks Infrequency of injection results in serum concentrations falling below therapeutic levels Target Therapeutic Concentration = .7 µg/ml Simulation based on ustekinumab published data (see Table 10 of BLA Number 125,261/ Supplement 150 of Janssen Biotech, Inc. submitted to FDA on September 30, 2019).
RaniPill + Ustekinumab Proposed Maintenance Dosing Concentration (µg/ml) Days Proposed RaniPill Dosing Target Therapeutic Concentration RaniPill may enable increased frequency of dosing which translates to: Lower peak-to-trough variability Tighter banding of therapeutic concentrations Simulation based on ustekinumab published data (see Table 10 of BLA Number 125,261/ Supplement 150 of Janssen Biotech, Inc. submitted to FDA on September 30, 2019).
Target Dosing: RaniPill + Ustekinumab Loading Phase Maintenance Phase DAILY 30-days of 7-12mg Daily Dosing Potential for better early-onset clinical efficacy 7-12mg 3-day Monthly Short Course Potential for tighter banding of therapeutic concentration levels MONTHLY Total of 36 pills per year per patient
Advantages of RaniPill Technology in Psoriasis Other Oral Options Less Efficacious than Biologics Otezla, JAK Inhibitors Additional Safety Concerns JAK Inhibitors Inconvenient Dosing BID Dosing Protagonist, Otezla Injectables Inconvenient & Painful to Administer Dosing Regimen not Maximizing Clinical Efficacy Higher AE Profile Significant Penalty for Lapses in Patient Adherence Efficacy Comparable to Injectable Biologics More Convenient than Other Oral Options Potentially Safer Product More Forgiving of Lapses in Patient Adherence RaniPill Targets
Rani - Confidential Celltrion Supply Agreement Includes ROFN Potential to Disrupt Billion-Dollar Markets with First Oral Option for Biologic Therapies in Psoriasis and Psoriatic Arthritis Ustekinumab Biosimilar (RT-111) Combining proven, high value drugs with competitive and disruptive technology Two partnerships that validate the RaniPill platform Adalimumab Biosimilar (RT-105) Lead Indication: Psoriasis Market Size: $9.7B in Stelara (ustekinumab) sales worldwide in 2022 (3) Lead Indication: Psoriatic Arthritis Market Size: $21.2B in Humira (adalimumab) sales worldwide in 2022 (4) 27
Target Product Profile of RaniPill Products Convenience Dosing Flexibility Patient Preference Of a Pill Efficacy Long Half-Life Safety Of a Monoclonal Antibody More convenient than small molecule Equal or better efficacy compared to injectables Potentially lower AEs than injectable biologics & small molecule Goals
Rani - Confidential Thank You
Additional Updates
Transenteric Delivery of GLP-1/GIP/Glucagon Molecule Elicits Rapid Weight Loss in Beagle Dogs Objective To evaluate the PK-PD profiles of Blinded Triagonist (a unimolecular incretin agonist for GLP-1, GIP and Glucagon receptors) in Beagle dogs delivered SC or via endoscopically guided transenteric injection (to mimic the Rani route of administration) Subjects Beagles, adult male, 11 - 13 kg, Total N=10 Test Groups Group 1 Transenteric (N=5): Triagonist, 0.12mg/kg (0.05ml/kg) injected via endoscopic access Group 2 SC (N=5): Triagonist, 0.12mg/kg (0.04ml/kg) injected subcutaneously Protocol All animals were dosed after an overnight fast Over 2 weeks, fasted body weights were taken, and blood samples were serially collected for tracking serum drug concentrations and various PD & safety biomarkers D Body Weight (%) Group 1: Endoscopic Group 2: SC D Serum Cholesterol (%) D Serum Triglycerides (%) All data are Means ± SE
Rani - Confidential Obesity Market Potential Opportunity Significant Potential Opportunity to Capture Portion of Obesity Market Based on Competitive Landscape (5) Wegovy Mounjaro Retatrutide Oral Semaglutide Orfoglipron Danuglipron Potential RaniPill Opportunity Administration SC SC SC Oral Oral Oral Oral Frequency Weekly Weekly Weekly Daily Daily Twice Daily Daily or Weekly Target GLP-1 Dual Agonist Triagonist GLP-1 GLP-1, small molecule GLP-1, small molecule Single, Dual and Triagonist Dosing 2.4mg weekly 15mg weekly 12mg weekly 50mg daily 45mg daily 120mg twice daily Comparable to SC Mean Body Weight Loss 15% 21% 24% 15% 15% NA Targeting Comparability to SC Discontinuation 7% 7% 6-16% 6% 10-17% 34% Targeting Similar to SC 32 SC = subcutaneous
Appendix
RT-111 Phase 1 Additional Data
Study Demographics – RT-111 Phase 1 Study BMI, Height and Weight data are Mean ± SD 35 SC 0.50 mg RT-111 0.50 mg RT-111 0.75 mg N 15 20 20 Mean Age, years 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) Body Mass Index (kg/m2) 23.8 ± 3.4 25.5 ± 3.7 22.9 ± 2.2 Height (cm) 172.7 ± 9.8 172 ± 9.7 170.2 ± 8.7 Weight (kg) 71.1 ± 12.7 76 ± 16.5 66.5 ± 9.5
PK Profiles of Oral Ustekinumab Biosimilar (RT-111) vs SC Stelara Injection Data are Means ± SEM. Data are pending final QA review. SC 0.50 mg RT-111 0.50 mg RT-111 0.75 mg Cmax (ng/ml) 58 ± 6 67 ± 7 93 ± 12 Tmax (days) 10.2 ± 0.9 3.2 ± 0.2 3.1 ± 0.4 AUC (day*ng/mL) 1,678 ± 112 1,365 ± 142 1,883 ± 162 SC 0.50 mg RT-111 0.50 mg RT-111 0.75 mg Cmax (ng/ml) 56 ± 4 67 ± 7 92 ± 8 Tmax (days) 10 ± 0.8 3.1 ± 0.2 3.3 ± 0.2 AUC (day*ng/mL) 1,566 ± 130 1,315 ± 150 1,814 ± 165
(1) Data of third party molecules are from separate studies published or disclosed by such third parties. Data are not from head-to-head studies. For Humira data and PASI 75 at 16 weeks, see tables 17-18 in U.S. prescribing information. For Humira PASI 75 at 48 weeks, see Table 3 of EMA Summary of Product Characteristics for Tremfya 100mg pre-filled pen and 100mg pre-filled syringe .For Humira revenues and Skyrizi revenues, see AbbVie press release dated February 9, 2023 (AbbVie Reports Full-Year and Fourth-Quarter 2022 Financial Results). For Cosentyx data and PASI 75 at 12 weeks, see U.S. prescribing information and for PASI 75 at 52 weeks for 300mg dose, see Table 4 in EMA Summary of Product Characteristics for Cosentyx 75mg. For Cosentyx revenues, see Novartis In Society Integrated Report 2022, Financial Performance..For Taltz data and PASI 75 data at 12 weeks, see U.S. prescribing information. For Taltz PASI 75 at 60 weeks, see Table 5 of EMA Summary of Product Characteristics for Taltz 80mg pre-filled syringe. For Taltz revenues, see Lilly press release dated February 2, 2023 (Lilly Reports Fourth-Quarter 2022 Financial Results, Core Business Growth and Pipeline Advancements Support Strong Long-Term Outlook). For Skyrizi data , see U.S. prescribing information. For Skyrizi PASI 75 at 12 weeks and 52 weeks, see Table 2 of EMA Summary of Product Characteristics for Skyrizi 150 mg pre-filled pen, and 75mg and 150mg pre-filled syringes. For Tremfya data and PASI 75 data at 16 weeks, see U.S. prescribing information. For Tremfya PASI 75 at 48 weeks, see Table 3 of EMA Summary of Product Characteristics for Tremfya 100mg pre-filled pen and 100mg pre-filled syringe. For Tremfya revenues, see DrugAnalyst market research database. For Stelara data and PASI 75 at 12 weeks, see U.S. prescribing information. For Stelara PASI 75 at 52 weeks, see EMA Summary Product Characteristics for Stelara 45mg and 90mg pre-filled pens. For Stelara revenues, see J&J annual earnings report for 2022. (2) Data of third party molecules are from separate studies published or disclosed by such third parties. Data are not from head-to-head studies. For Otezla PASI data, see Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1), Papp et al, Journal of the American Academy of Dermatology, Volume 73, Issue 1, P37-49, July 2015. For Otezla revenue, see Amgen press release dated January 31, 2023 (Amgen Reports Fourth Quarter and Full Year 2022 Financial Results). For Otezla pill number, see Otezla U.S. prescribing information. For Sotyktu PASI data, see Bristol Myers Squibb press release dated October 11, 2023 (Sotyktu (deucravacitinib) Long-Term Data Demonstrate Durable Efficacy and Consistent Safety for up to Three Years in Moderate-to-Severe Plaque Psoriasis. For Sotyktu revenue, see Bristol Myers Squibb quarterly earnings press releases dated April 27, 2023, July 27, 2023, and October 26, 2023. For Sotyktu pill number, see Sotyktu U.S. prescribing information. For JNJ-2113 (PTG-200), PASI 75 scores are for 100mg dose (daily and twice daily); see Johnson & Johnson press release dated July 4, 2023 (Janssen Announces Positive Topline Results for JNJ-2113 - a Novel, First and Only Oral IL-23 Receptor Antagonist Peptide in Development for Moderate-to-Severe Plaque Psoriasis). (3) Johnson & Johnson 2022 Annual Report. (4) Abbvie 2022 Annual Report. (5) Data of third party molecules are from separate studies published or disclosed by such third parties. Data are not from head-to-head studies. For Wegovy, see prescribing information. For Mounjaro, see prescribing information and press release Lilly's tirzepatide delivered up to 22.5% weight loss in adults with obesity or overweight in SURMOUNT-1, Eli Lilly and Company, April 28, 2022. For oral semaglutide, The Lancet, Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomized, double-blind, placebo-controlled, phase 3 trial, Knop et al, June 26, 2023, Doi.org/10.1016/ S0140-6736(23)01185-6. For retatrutide, (dosing and weight loss) press release, Lilly’s phase 2 retatrutide results published in The New England Journal of Medicine show the investigational molecule achieved up to 17.5% mean weight reduction at 24 weeks in adults with obesity and overweight, Eli Lilly & Company, June 26, 2023. (Discontinuation) New England Journal of Medicine, Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial, Jastreboff et al, June 26, 2023, DOI: 10.1056/NEJMoa2301972. For orfoglipron, (Dosing and weight loss) New England Journal of Medicine, 389:877-888, DOI: 10.1056/NEJMoa2302392, September 7, 2023. (Discontinuation) New England Journal of Medicine, Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity, Wharton et al, June 23, 2023, DOI: 10.1056/NEJMoa2302392. For danuglipron, (discontinuation rate) Everyday Health, Could This Pill Be the Next Ozempic?, Ross Wollen, May 22, 2023. (Dosing) JAMA Network Open 2023;6(5):e2314493. Doi:10.1001/jamanetworkopen.2023.14493. References