Sorrento Releases Positive Topline Results from the Phase I Study Completed in Australia and Preliminary Results from a Phase Ib Study in China with STI-1558, an Oral M(pro) Inhibitor as a Standalone Treatment for COVID-19 without the Need for Ritonavir Boosting

Rhea-AI Summary

Sorrento Therapeutics (Nasdaq: SRNE) announced the availability of topline safety and pharmacokinetic data from its Phase I study of STI-1558, an oral M^pro inhibitor for COVID-19, conducted in 58 healthy volunteers in Australia. The study showed STI-1558 was well-tolerated with no severe adverse events. The pharmacokinetic profile demonstrated dose proportionality, and trough levels were significantly above the effective concentration for viral inhibition. A similar study in China is underway, and Phase II/III trial protocols have been submitted to regulatory agencies, including the US FDA.

Positive

• STI-1558 was well-tolerated with no severe adverse events and no dose limiting toxicity.
• Pharmacokinetic data showed dose proportionality; trough levels significantly exceeded the EC₉₀ value for viral inhibition.
• Successful Phase I study supports the advancement of Phase II/III trials for COVID-19 treatment.

Negative

• Mild to moderate liver enzyme elevations were observed in the highest dose cohort, raising some safety concerns.

• Topline safety and pharmacokinetic (PK) data from the Phase I single ascending dose (SAD)/multiple ascending dose (MAD) study of STI-1558 in 58 healthy volunteers in Australia are now available. The SAD portion of the study evaluated doses from 300 mg to 2,000 mg and the MAD portion evaluated 300 mg, 600 mg or 800 mg BID (twice a day daily) for 7.5 days.
• Overall, STI-1558 was well-tolerated at these doses with most subjects reporting no adverse events (AEs). There was no dose limiting toxicity during the study. There were no severe or serious AEs, no premature discontinuation of STI-1558 due to an AE, and no deaths. Most AEs were mild and unrelated. The PK profile was dose proportional; the mean AUC (h*µg/mL) in the SAD 300 mg, 600 mg, 1200 mg and 2000 mg cohorts was 14.3, 29.2, 43.8 and 93.3, respectively. In the MAD cohorts (300 mg BID, 600 mg BID and 800 mg BID), no accumulation was seen and trough concentrations (C_trough) were 225 ng/mL, 475 ng/mL and 506 ng/mL, respectively. Even the lowest dose produced trough levels significantly above the EC₉₀ value for viral inhibition of STI-1558. These data confirm adequate blood levels were achieved without the need for Ritonavir.
• A similar Phase I/Ib SAD/MAD study has been fully enrolled in China in both healthy subjects and patients infected with SARS-CoV-2. The PK profile in China was similar to that seen in Australia. Preliminary safety and efficacy data found that the safety profile was comparable between healthy uninfected subjects and infected subjects and that STI-1558 resulted in a dramatic rapid reduction in viral load.
• Phase II/III protocols of STI-1558 600 mg BID for 5 days as a standalone treatment of COVID-19 have been submitted to various regulatory agencies including the US FDA, Mexico COFEPRIS and China.
• Testing to date has demonstrated that the antiviral activity of STI-1558 on the M^pro protein is not impacted by the spike mutations of emerging variants NMPA.
  

SAN DIEGO, Nov. 29, 2022 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") today released topline Phase I SAD/MAD study data of its oral main protease (M^pro) inhibitor, STI-1558, conducted in 58 healthy volunteers in Australia. In addition to the M^pro inhibition, which can block viral replication, STI-1558 also has cathepsin L inhibition, which can prevent viral entry into the host cell. Testing to date has demonstrated that the activity of STI-1558 on the M^pro protein is not impacted by the spike mutations of emerging variants.

The Phase I safety and PK study (MPR-COV-101AU) is entitled: “A Randomized, Double-Blind, Placebo-Controlled, Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of STI-1558 in Healthy Volunteers”. In the SAD portion of the study, 4 dose-escalation cohorts (single oral dose of 300 mg, 600 mg, 1200 mg, and 2000 mg STI-1558 or placebo) were conducted with 8 subjects in each cohort-randomized 3:1 (active:placebo, except for cohort 2 for the fasted and fed dosing, with 10 subjects randomized 4:1). In the MAD portion of the study, 3 dose-escalation cohorts with daily doses of 300 mg BID, 600 mg BID or 800 mg BID for 7.5 days (total 15 doses) were conducted with 8 subjects in each dose cohort randomized 3:1 (active:placebo). Subjects remained at the facility for the entire treatment period.

Topline safety and PK data from the SAD and MAD portions of the study are now available. Overall, there were no changes in vital signs, physical examinations, or ECGs resulting from study participation. STI-1558 was well-tolerated at the doses studied, with most subjects reporting no AEs. There was no dose limiting toxicity and no severe or serious adverse events (AEs), premature discontinuation of STI-1558 due to an AE, or deaths. Most AEs were mild and unrelated.

A total of 11 subjects reported an AE in the SAD part of the study, with 3 AEs of headache deemed related to STI-1558 (one moderate severity in the 600 mg cohort and two mild cases in the 1200 mg cohort), possibly due to restricted caffeine intake. In the MAD part of the study, 13 subjects reported AEs, with only two subjects experiencing related events of mild or moderate liver enzyme elevation (ALT/AST) without bilirubin elevation in the highest dose cohort, 800 mg BID, which is 33% higher for 50% longer than the planned treatment regimen for Phase II, 600 mg BID for 5 days. The liver enzyme elevations occurred late (≥ 5 days) in study treatment and resolved without the need for any treatment.

The PK plots for SAD doses of 300 mg, 600 mg, 1200 mg and 2000 mg displayed dose proportionality with AUC (h*µg/mL) of 14.3, 29.2, 43.8 and 93.3, respectively. Trough levels (C_trough) during the MAD dosing were 225 ng/mL, 475 ng/mL and 506 ng/mL, respectively, which are significantly above the EC₉₀ value predicted for viral inhibition by various preclinical models. Observed half lives during the SAD/MAD dosing support BID dosing. These data demonstrate that STI-1558 can be a potential treatment for COVID-19 without the need for Ritonavir boosting. Additionally, in preclinical studies, STI-1558 is neither a CYP3A4 inhibitor nor inducer, which suggests a low risk of CYP3A4 related drug-drug interactions. Based upon the safety and PK profiles, a 600 mg BID dose for 5 days has been selected as the recommended dose for Phase II/III studies to treat mild-to-moderate COVID-19 in outpatients.

The enrollment of a Phase I trial in participants infected with SARS-CoV-2 was completed in China (MPR-COV-101CN), and a total of 78 participants (32 in SAD and 46 in MAD) were enrolled to assess the PK, safety, tolerability and efficacy in a SAD part of the study in healthy volunteers (300 mg, 600 mg, 1200 mg and 2000 mg, 8 subjects in each cohort at 3:1, active: placebo) and in a MAD part of the study in participants infected with SARS-CoV2 (300 mg BID, 600 mg BID and 800 mg BID daily for 7.5 days). Preliminary PK data in the SAD portion of the study demonstrated a similar PK profile between the Australia trial and the China trial. Preliminary efficacy data showed a 3-log₁₀ reduction by day 3 in viral RNA load in participants infected with SARS-CoV2 by quantitative PCR.

“The unblinded safety and PK data in the Australia trial and the preliminary efficacy data from the China trial in participants infected with SARS-CoV-2 are very encouraging, and we are engaging with regulatory agencies on global Phase II/III trial design in order to initiate the STI-1558 Phase II/III trials in Mexico, the US and China as soon as possible,” stated Henry Ji, Ph.D., President and CEO of Sorrento.

About Sorrento Therapeutics, Inc. 

Sorrento is a clinical and commercial stage biopharmaceutical company developing new therapies to treat cancer, pain (non-opioid treatments), autoimmune disease and COVID-19. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as next-generation tyrosine kinase inhibitors (“TKIs”), fully human antibodies (“G-MAB™ library”), immuno-cellular therapies (“DAR-T™”), antibody-drug conjugates (“ADCs”), and oncolytic virus (“Seprehvec™”). Sorrento is also developing potential antiviral therapies and vaccines against coronaviruses, including STI-1558, COVISHIELD™ and COVIDROPS™, COVI-MSC™; and diagnostic test solutions, including COVIMARK™.

Sorrento's commitment to life-enhancing therapies for patients is also demonstrated by our effort to advance a TRPV1 agonist, non-opioid pain management small molecule, resiniferatoxin (“RTX”), and SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (SEMDEXA™), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, and to commercialize ZTlido^® (lidocaine topical system) 1.8% for the treatment of postherpetic neuralgia (PHN). RTX has been cleared for a Phase II trial for intractable pain associated with cancer and a Phase II trial in osteoarthritis patients. Positive final results from the Phase III Pivotal Trial C.L.E.A.R. Program for SEMDEXA™, its novel, non-opioid product for the treatment of lumbosacral radicular pain (sciatica), were announced in March 2022. ZTlido^® was approved by the FDA on February 28, 2018.

For more information visit www.sorrentotherapeutics.com

Forward-Looking Statements

This press release and any statements made for and during any presentation or meeting contain forward-looking statements related to Sorrento Therapeutics, Inc., under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding STI-1558, including its potential to block viral replication or prevent viral entry into the host cell, the recommended dose for Phase II/II studies to treat mild-to-moderate COVID-19 in outpatients, preliminary efficacy data for the Phase I trial in participants infected with SARS-CoV-2 in China, the potential appropriateness of STI-1558 as a standalone treatment for COVID-19, and the potential initiation of the STI-1558 Phase II/III trials in Mexico, the US and China and the expected timing thereof. Risks and uncertainties that could cause our actual results to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: risks related to Sorrento's technologies and prospects, including, but not limited to risks related to safety and efficacy of STI-1558 and seeking regulatory approval for STI-1558; clinical development risks, including risks in the progress, timing, cost, and results of clinical trials and product development programs; risks of difficulties or delays in obtaining regulatory approvals; risks that clinical study results may not meet any or all endpoints of a clinical study and that any data generated from such studies may not support a regulatory submission or approval; risks that prior test, study and trial results, including those for STI-1558 and any topline or preliminary results, may not be replicated in continuing or future studies and trials; risks of manufacturing and supplying drug product; risks related to leveraging the expertise of its employees, subsidiaries, affiliates and partners to assist Sorrento in the execution of its product candidates’ strategies; risks related to the global impact of COVID-19; and other risks that are described in Sorrento's most recent periodic reports filed with the Securities and Exchange Commission, including Sorrento's Annual Report on Form 10-K for the year ended December 31, 2021 and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and we undertake no obligation to update any forward-looking statement in this press release except as required by law.

Media and Investor Relations
Contact: Brian Cooley
Email: mediarelations@sorrentotherapeutics.com

Sorrento^® and the Sorrento logo are registered trademarks of Sorrento Therapeutics, Inc.

G-MAB™, DAR-T™, Seprehvec™, SOFUSA™, COVISHIELD™, COVIDROPS™, COVI-MSC™, COVIMARK™ and Fujovee™ are trademarks of Sorrento Therapeutics, Inc.

SEMDEXA™ (SP-102) is a trademark of Semnur Pharmaceuticals, Inc. A proprietary name review by the FDA is planned.

ZTlido^® is a registered trademark owned by Scilex Pharmaceuticals Inc.

All other trademarks are the property of their respective owners.

©2022 Sorrento Therapeutics, Inc. All Rights Reserved.

FAQ

What are the findings from Sorrento's STI-1558 Phase I study?

The study demonstrated STI-1558's good tolerance among participants with no serious adverse events, and a favorable pharmacokinetic profile.

What are the next steps for STI-1558 following the Phase I trial?

Phase II/III protocols for STI-1558 have been submitted to regulatory agencies, including the US FDA, focusing on its use as a standalone treatment for COVID-19.

What does the pharmacokinetic data indicate about STI-1558?

The pharmacokinetic data suggests the drug maintains adequate blood levels without the need for Ritonavir boosting, with no accumulation seen in multiple dosing.

How does STI-1558 perform against COVID-19 variants?

STI-1558 has shown antiviral activity against the M^pro protein, indicating effectiveness against mutants as its activity is not impacted by spike mutations.

What preliminary efficacy results were reported for STI-1558?

In a concurrent trial in China, STI-1558 resulted in a dramatic reduction in viral load among infected participants.