8-K: Rani Therapeutics Announces Positive Topline Results for Oral Ustekinumab Biosimilar Phase 1 Trial

Rani Therapeutics reports successful Phase 1 trial results for its oral ustekinumab biosimilar, RT-111, showing high bioavailability and good tolerability.

Summary

• Rani Therapeutics has announced positive topline results from its Phase 1 clinical trial of RT-111, an oral capsule containing an ustekinumab biosimilar.
• The study was a single-center, open-label trial conducted in Australia with 55 healthy adult volunteers.
• Participants received either a 0.5mg or 0.75mg dose of RT-111 orally, or a 0.5mg subcutaneous injection of STELARA as a control.
• The study evaluated the safety, tolerability, and pharmacokinetics of RT-111.
• RT-111 demonstrated high bioavailability, estimated at 84% for the 0.5mg dose relative to the subcutaneous injection.
• The 0.5mg RT-111 group had a Cmax of 67 ng/mL and a Tmax of 3.1 days, while the 0.75mg group had a Cmax of 92 ng/mL and a Tmax of 3.3 days.
• The subcutaneous STELARA group had a Cmax of 56 ng/mL and a Tmax of 10 days.
• There were no serious adverse events reported in the study, and RT-111 was generally well-tolerated.
• The incidence of anti-drug antibodies was not significantly different between the RaniPill delivery route and the subcutaneous injection.
• Celltrion has a right of first negotiation to acquire worldwide rights to RT-111 following the successful completion of this Phase 1 trial.

Sentiment

Score: 9

Explanation: The document presents very positive results from a Phase 1 trial, with high bioavailability and good tolerability of the oral drug. The potential for disruption in the biologics market and the validation of the RaniPill technology are strong positives.

Positives

• The oral delivery of ustekinumab biosimilar via RaniPill achieved high bioavailability, comparable to subcutaneous injection.
• RT-111 was well-tolerated with no serious adverse events, indicating a good safety profile.
• The faster Tmax of oral RT-111 compared to subcutaneous injection could lead to a quicker onset of action.
• The successful completion of this Phase 1 trial validates Rani's RaniPill technology for oral delivery of biologics.
• The results suggest that RT-111 could offer a more convenient dosing option for patients compared to injections.
• The lack of significant difference in anti-drug antibody development is a positive sign for the long-term efficacy of the treatment.

Negatives

• Two subjects in the 0.5mg RT-111 group and one subject in the 0.5mg SC STELARA group had mild, transient adverse events.
• One subject reported a burning sensation in the stomach after taking the capsule, although this was not directly linked to drug deployment.

Risks

• The document contains forward-looking statements, and actual results may differ due to risks and uncertainties inherent in research and development.
• Initial clinical results may not be indicative of future clinical results.
• The company is subject to risks detailed in their SEC filings, including the annual report on Form 10-K.
• The company relies on third-party suppliers for manufacturing clinical supplies.
• There is a risk that the company will be unable to obtain necessary capital when needed on acceptable terms or at all.

Future Outlook

The company believes RT-111 has the potential to offer a differentiated dosing regimen for patients with psoriasis and is working towards making oral biologics a reality for millions of patients with autoimmune conditions. They are also planning to initiate Phase 2 trials for RT-102 in osteoporosis in 2024.

Management Comments

• Talat Imran, Chief Executive Officer of Rani, stated that RT-111 is the first ever oral monoclonal antibody to achieve high bioavailability in humans.
• Talat Imran also mentioned that the data provides clinical validation of their ability to transform an injectable large molecule into an oral pill.
• Management believes 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.

Industry Context

This announcement is significant as it demonstrates the potential for oral delivery of biologics, which could disrupt the market for injectable treatments for autoimmune conditions like psoriasis. The successful Phase 1 trial positions Rani as a potential leader in this space, competing with established injectable biologics and oral small molecules.

Comparison to Industry Standards

• The bioavailability of 84% for the 0.5mg dose of RT-111 is a significant achievement, as oral delivery of biologics has historically been challenging.
• The Tmax of 3.1-3.3 days for RT-111 is much faster than the 10 days for subcutaneous STELARA, potentially offering a quicker onset of action.
• The Cmax values for RT-111 are also higher than those for subcutaneous STELARA, suggesting a more effective delivery of the drug.
• Compared to other oral treatments for psoriasis like Otezla and Sotyktu, RT-111 aims to provide efficacy comparable to injectable biologics with the convenience of oral administration.
• The company is targeting a PASI 75 score of 81+% which is comparable to the efficacy of injectable biologics such as Humira, Cosentyx, Taltz, Tremfya, Skyrizi and Stelara.
• The company is also targeting a similar safety profile to injectable biologics, which would be an improvement over some oral treatments like JAK inhibitors.

Related Party Transactions

• The ustekinumab biosimilar used in RT-111 is manufactured and supplied by Celltrion under Rani's License and Supply Agreement.

Stakeholder Impact

• Shareholders may view the positive trial results as a positive development for the company's future prospects.
• Patients with autoimmune conditions may benefit from a more convenient oral treatment option.
• Employees may be encouraged by the progress of the company's technology.
• Celltrion, as a partner, may benefit from the potential commercial success of RT-111.

Next Steps

• Rani plans to initiate Phase 2 trials for RT-102 in osteoporosis in 2024.
• Celltrion has a right of first negotiation to acquire worldwide rights to RT-111 following the successful completion of this Phase 1 trial.

Key Dates

Keywords

RaniPill, ustekinumab, biosimilar, RT-111, oral delivery, biologics, Phase 1 trial, bioavailability, pharmacokinetics, psoriasis, Celltrion