Sorrento Therapeutics has received clearance from the U.S. Food and Drug Administration (FDA) to start phase I clinical trials for its investigational new drug (IND) application for STI-6129, a CD38-targeting antibody-drug conjugate (ADC).

STI-6129 is based on multiple technology platforms that are under development by Sorrento Therapeutics, including the company’s CD38 specific antibody identified from its fully human G-MAB™ antibody library, its proprietary drug payload Duostatin 5 and the site-specific C-LOCK conjugation technology.

Henry Ji, Ph.D., the Chairman, President and Chief Executive Officer of Sorrento Therapeutics has more than 25 years of experience in the biotechnology and life sciences industry. He co-founded Sorrento and has served as the company's director since 2006. (CEO and President since 2012, and Chairman since 2017). Photo Courtesy: © 2017 - 2020 Sorrento Therapeutics.
Henry Ji, Ph.D., the Chairman, President, and Chief Executive Officer of Sorrento Therapeutics has more than 25 years of experience in the biotechnology and life sciences industry. He co-founded Sorrento and has served as the company’s director since 2006. (CEO and President since 2012, and Chairman since 2017). Photo Courtesy: © 2017 – 2020 Sorrento Therapeutics.

“[The FDA clearance of] our STI-6129 IND application, allowing us to proceed to first-in-human clinical trials, is another important milestone for Sorrento,” stated Dr. Henry Ji, Ph.D., Chairman, and Chief Executive Officer of Sorrento Therapeutics.

“Together with our CD38 CAR T-cell program, this has the potential to provide additional therapeutic options for patients in need. We are looking forward to further evaluating the safety and efficacy of STI-6129 in clinical trials.”

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Study design
Sorrento intends to initiate a phase I multicenter, open-label, dose-escalation clinical trial in patients with advanced relapsed and/or refractory systemic amyloid light-chain (AL) amyloidosis with a primary objective to identify a phase II dose for STI-6129 based on its safety, preliminary efficacy and pharmacokinetic profile.

This study includes three dosing plan stages. The initial stage of the trial is the dose-escalation stage using a standard dose-escalation 3+3 design to identify a safe maximum tolerated dose (MTD) of STI-6129 in patients with relapsed or refractory systemic AL amyloidosis.

After identification of the MTD, the investigators will establish the best-tolerated dose, (i.e., the maximum practical dose or MPD]).  This phase of the trial is expected to enroll 12 patients and is designed to collect pharmacokinetic data to model a treatment schedule that achieves a stable effective serum concentration. Following the dose-escalation stage and the pharmacokinetic stage, investigators will analyze the results to develop a treatment dose/schedule for treating 30 additional patients enrolled in the expansion stage.

Each patient enrolled in the trial will receive up to three 3-week cycles (Q3W) of STI-6129. After the treatment, all patients will be monitored bi-monthly for up to a year.

A rare disease
Amyloidosis is a rare disease, affecting less than 200,000 patients in the United States, that occurs when an abnormal protein, called amyloid, builds up in the patient’s organs and interferes with the normal organ function. Organs that may be affected include the heart, kidneys, liver, spleen, nervous system, and digestive tract.

Although the symptoms of the disease depend on which organs are affected, they generally include swelling, fatigue and weakness, shortness of breath, and numbness, tingling, or pain in the hands or feet. Treatments options may include steroids, immunosuppressive drugs, chemotherapy, or a stem-cell transplant, similar to that used to combat cancer.

Hui Li, Ph.D. is Senior Vice President responsible for Sorrento’s partnerships and licensing negotiations, as well as operation of Sorrento’s Chinese subsidiaries. Prior to joining Sorrento, he was Chief Executive Officer at Levena BioPharma, a biotech company focused on antibody-drug conjugate (ADC) discovery and production. Before Levena, he held senior management roles as the head of Business Development at PDD and BioDuro. Li spent 10 years at Pfizer Global Research & Development, La Jolla Laboratories and has led research programs in a number of disease areas including oncology, metabolic diseases, anti-viral, and ophthalmology. Photo Courtesy: © 2017 - 2020 Sorrento Therapeutics.
Hui Li, Ph.D. is Senior Vice President responsible for Sorrento’s partnerships and licensing negotiations, as well as operation of Sorrento’s Chinese subsidiaries. Prior to joining Sorrento, he was Chief Executive Officer at Levena BioPharma, a biotech company focused on antibody-drug conjugate (ADC) discovery and production. Before Levena, he held senior management roles as the head of Business Development at PDD and BioDuro. Li spent 10 years at Pfizer Global Research & Development, La Jolla Laboratories and has led research programs in a number of disease areas including oncology, metabolic diseases, anti-viral, and ophthalmology.
Photo Courtesy: © 2017 – 2020 Sorrento Therapeutics.

First ADC to use C-LOCK conjugation
“This is Sorrento’s first ADC utilizing our site-specific C-LOCK conjugation technology that is advancing into clinical evaluation,” Hui Li, head of Sorrento’s ADC business unit, Levena Biopharma.

“STI-6129 demonstrated an improved therapeutic index in animal models, as compared to traditional non-selective conjugates, and we look forward to potentially expanding its utilization into additional ADC programs.”

G-MAB™ Technology
Sorrento’s proprietary G-MAB™ technology, invented by Ji, is based on RNA transcription for amplification of the antibody variable domains from over 600 different donors. Using in-depth analysis, deep sequencing DNA data showed that the G-MAB library contains more than 1016 (quadrillion) distinct antibody sequences. This makes Sorrento’s G-MAB™ one of the largest fully human antibody libraries in the biopharmaceutical industry. Using this unique library, Sorrento Therapeutics has successfully identified fully human antibodies against over 100 clinically-relevant high-impact oncogenic targets, including PD-1, PD-L1, CD38, CD123, CD47, VEGFR2, and CCR2.

Development facilities
To secure the development and manufacturing of  STI-6129 and other investigational agents, Sorrento Therapeutics currently has a cGMP facility in Suzhou, in the southeastern Jiangsu Province of Eastern China, about 62 miles (100 kilometers) northwest of Shanghai.  This facility, which operates under the Levena Biopharma brand name, has been in operation since 2016 and is designed to support clinical cGMP production of drug linkers as well as antibody conjugation. With full analytical support capabilities and a facility equipped to handle highly potent API (isolator), the site has supported over 20 clinical batches for clinical trials worldwide.

Clinical trials
Anti-CD38-Duostatin 5.2 ADC for AL Amyloidosis – NCT04316442