Sutro ADC Targeting CD74 Eradicates B-Cell Hematologic Malignancy, Prolongs Survival in Tumor Models
SOUTH SAN FRANCISCO, April 3, 2017 – STRO-001, an antibody drug conjugate developed by Sutro Biopharma Inc., demonstrated potent anti-tumor activity in multiple myeloma, diffuse large B-cell lymphoma and mantle cell lymphoma tumor models while reducing the potential for toxic secondary effects on adjacent healthy cells, according to findings presented this past Sunday at the American Association for Cancer Research’s annual meeting in Washington, DC.
STRO-001, an antibody drug conjugate, or ADC, that targets CD74, a protein highly expressed in hematologic B-cell malignancies, eradicated malignant plasma B-cells in the multiple myeloma MM.1S xenograft model, enabling all mice treated with the compound to survive and remain tumor-free until completion of the four-month study, compared to mice treated with placebo, all of whom died within 35 days of initial treatment.
The Sutro ADC also demonstrated potent anti-tumor activity in a mouse diffuse large B-cell lymphoma tumor model when administered with standard of care chemotherapy, according to the AACR poster presentation.
In addition, researchers reported the first evidence that STRO-001 significantly inhibits tumor growth in a Jeko-1 mantle cell lymphoma mouse model and presented pharmacodynamic evidence of B-cell targeting from an exploratory toxicology study in cynomolgus monkeys.
Sutro plans to submit an IND to the Food & Drug Administration at the end of 2017 and to commence clinical testing of STRO-001 in the first quarter of 2018.
“These findings add to previous evidence of STRO-001’s potent in vitro cytotoxicity in multiple malignant B-cell lines,” Sutro CEO Bill Newell said. “We first presented research showing efficient cell killing and potent anti-tumor activity in mouse tumor models of non-Hodgkin lymphoma and multiple myeloma at the December 2016 American Society of Hematology annual meeting.”
Preventing the ‘Bystander Effect’
“STRO-001 was developed with Sutro’s proprietary cell-free protein synthesis and site-specific conjugation platforms, which facilitate multiple rounds of antibody and ADC optimization,” said Dr. Arturo Molina, a medical oncologist and Sutro’s chief medical officer.
“Sutro’s Xpress CF+™ platform enables it to produce novel ADCs that directly target cancer cells and avoid a toxic ‘bystander effect’ on adjacent healthy cells,” he added.
Unlike conventional cell-based expression systems, Sutro’s technology isolates a cell’s protein production machinery into a cell-free extract, Xtract CF™, which includes all the necessary biochemical components for energy production, transcription and translation. The Xpress CF+™ platform further supports incorporation of non-natural amino acids in specific positions in the protein of interest, allowing for site-specific conjugation of cytotoxins and the creation of homogeneous ADCs. This process is capable of producing single proteins at large scale within 24 hours, unconstrained by cellular structures and their limitations.
Sutro’s manufacturing facility in San Carlos, California, is built to maximize the speed and efficiency of cell-free extract and protein production. The cell-free extract is manufactured by a multi-day continuous process producing extract for large scale Xpress CF+™ reactions.
About Sutro Biopharma
Sutro Biopharma Inc., located in South San Francisco, develops best-in-class antibody drug conjugate (ADC) and multi-specific antibody-based therapeutics for cancer therapy, including immuno-oncology therapies. Sutro’s discovery and development efforts are driven by its proprietary Xpress CF+™ platforms, a biochemical synthesis system that enables rapid and systematic evaluation of protein structure-activity relationships, as well as rapid and predictable scalability for manufacturing in Sutro’s facility. In addition to developing its own drug candidate pipeline, which is focused on mono- and bi-specific ADCs, Sutro is collaborating with select pharmaceutical and biotech companies to discover and develop novel therapeutics.