Sorrento Successfully Completes Phase 1 Study and Is Proceeding to Implement Global Registrational Trials with STI-1558, an Oral Mpro Inhibitor as a Standalone Oral Treatment and Prevention of COVID-19 without the Need for a Ritonavir Booster
- Phase 1 Study (with 58 healthy volunteers) of STI-1558 was completed in Australia with 300 mg, 600 mg, 1,200 mg and 2,000 mg doses in the single ascending dose (SAD) portion of the study and 300 mg, 600 mg and 800 mg BID (twice a day) daily for 7.5 days in the multiple ascending dose (MAD) portion of the study.
- The pharmacokinetics (PK) were dose proportional in the SAD study. In the MAD study, the 600 mg BID dose cohort achieved trough concentrations (Ctrough) significantly above the EC90 value for viral inhibition by STI-1558 and no accumulation was seen in the subjects, supporting a 600 mg twice daily dose for 5 days as the recommended dose for standalone treatment without ritonavir as booster.
- There were no serious adverse events (SAEs) or severe treatment emergent adverse events (TEAEs) and the maximum tolerated dose (MTD) was not reached in either the SAD (up to 2000 mg) or the MAD (up to 800 mg BID daily for 7.5 days) portions of the study.
- Global registrational Phase 2/3 trials of STI-1558 as a standalone treatment of COVID-19 are proceeding and are expected to be implemented rapidly in the US, Mexico, China, Australia and other regions.
SAN DIEGO, Oct. 17, 2022 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") today announced the completion of a Phase 1 study of its oral main viral protease (Mpro) inhibitor, the STI-1558 in 58 healthy volunteers.
The Phase 1 safety and PK study in healthy volunteers was conducted in Australia. The 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 an additional cohort at the Cohort 2 dose for the PK of 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 consecutive 7.5 days (total 15 doses) were conducted with 8 subjects in each dose cohort randomized 3:1 (active:placebo).
The preliminary blinded safety and PK data from the SAD and MAD portions of the study are available. Overall, there were no changes in vital signs, physical examinations, ECGs or safety clinical labs resulting from study participation. The preliminary summary of treatment-emergent adverse events (TEAEs) showed that there were no serious AEs (SAEs) or severe TEAEs and the maximum tolerated dose was not reached in either the SAD or MAD portions of the study. No dose limiting toxicities were noted and there were no premature terminations from the study post-treatment.
The linear and semi-log plots for doses from 300 mg to 2000 mg (Cohorts 1-4) are proportional in the SAD portion. In the 600 mg BID dose cohort of the MAD portion, the trough concentration (Ctrough) was significantly above the EC90 value of predicted value for viral inhibition and no accumulation was seen, supporting a 600 mg twice-daily dose as a recommended dose for standalone treatment without ritonavir booster. In preclinical study, STI-1558 has shown sufficient lung tissue penetration and dual inhibition of Mpro for viral replication and cathepsin L for viral entry to host cells, indicating a potential robust antiviral activity in COVID-19 patients.
A phase 1 trial in participants infected with SARS-CoV-2 has been initiated in China (MPR-COV-101CN), and a total 56 participants will be enrolled to assess the safety, tolerability, and efficacy in 3 MAD dose cohorts (300 mg BID, 600 mg BID and 800 mg BID daily for 7.5 days). Eight participants infected with SARS-CoV-2 in the first MAD dose cohort of 300 mg BID have been dosed.
A large Phase 2 registrational study is planned in Mexico that could support an Emergency Use Authorization (EUA) in Mexico with potential for distribution throughout Latin America. Registrational Phase 2/3 trials in US, China and other major regions have also been planned.
“The successful completion of the Phase 1 in Australia allows us to move STI-1558 forward quickly with registrational Phase 2/3 studies in the US, Mexico, and China,” stated Henry Ji, Ph.D., Chairman, President and CEO of Sorrento. “These results confirm the pharmacokinetics for this antiviral treatment are appropriate for a standalone treatment for COVID patients.”
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™; 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.
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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 the preliminary data and results from the SAD and MAD portions of the Phase 1 study, the phase 1 trial in China in participants infected with SARS-CoV-2, the Phase 2 registrational study planned in Mexico, any possible EUA for STI-1558 in Mexico and any potential for distribution throughout Latin America, the Company’s plans to conduct and move forward with Phase 2/3 trials in US, China and other major regions and the potential appropriateness of STI-1558 as a standalone treatment for COVID patients. 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; risk 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, 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.
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