Sutro Biopharma, a biotechnology company developing best-in-class antibody drug conjugate (ADC) and multi-specific antibody-based therapeutics for cancer therapy, including immune-oncology therapies has launched IND-enabling studies, including preparation for GLP toxicology, of SP7675, also known as STRO-001.

Recently completed studies show that STRO-001, an antibody drug conjugate targeting CD74.  The ADC is based on Sutro’s lead antibody (SP7219) conjugated to non-cleavable DBCO-maytansinoid linker-warheads with an average drug-antibody ratios (DAR) of 2.

In the development of the investigational antibody-drug conjugate, scientists used a site-specific conjugation technology which results in a high degree of homogeneity characterized by the drug linker covalently binding to a single defined site. The sites for conjugation were selected based on highest cell killing activity and stablity in vitro and in vivo.

The agent has demonstrated efficient cell killing in multiple malignant B-cell lines and exhibited potent anti-tumor activity in six mouse tumor models of non-Hodgkin lymphoma and multiple myeloma.

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Adrianna Rossi,M.D. New York, New York is all smiles as she takes in the Exhibits Opening with thousands of ASH attendees.
Photo 1.0: Adrianna C. Rossi, M.D., a hematologist in New York affiliated with NewYork-Presbyterian/Weill Cornell, is all smiles as she takes in the Exhibits Opening with thousands of attendees during the 58th Annual Meeting of the American Society of Hematology, held December 3 – 6, 2016 in San Diego, CA. Courtesy: © ASH/American Society of Hematology. Used with permission.

Targeting CD74
CD74, also known as HLA-DR-associated invariant chain, a type II transmembrane glycoprotein involved in the formation and transport of MHC class II protein, is highly expressed in B-cell malignancies.

Arturo Molina, M.D., a medical oncologist and Sutro’s chief medical officer, described the study findings this past Sunday in an oral presentation during the 58th Annual Meeting of the American Society of Hematology, being held in San Diego, CA, December 3 – 6, 2016. [1]

Molina noted that the in vitro cytotoxicity assays shows nanomolar potency of STRO-001 in four Multiple Meyloma cell lines: Mc/CAR (IC50 0.8 nM), MM.1S (IC50 10-11 nM), U266B1 (IC50 8.5 -9.3 nM), and ARP-1 (IC50 4.3-22 nM). While CD74 cell surface expression is required for ADC anti-proliferative effect but the actual expression level does not seem to correlate with in vitro potency. STRO-001 inhibited the formation of internal visceral tumors in the ARP-1 xenograft model after 3 weekly doses of 3 mg/kg.

Poster Presentation
The Sutro STRO-001 research team presented additional findings yesterday in a poster. [2]

“Based on these findings, we are launching IND-enabling and GLP toxicology studies of an ADC developed with Sutro’s proprietary cell-free protein synthesis and site-specific conjugation platforms, which facilitate multiple rounds of antibody and ADC optimization,” Sutro CEO Bill Newell said.

“With these data, we have encouraging preclinical evidence of CD74’s potential usefulness as an ADC target,” added Amrita Krishna, M.D., Professor of Hematology and Hematopoietic Cell Transplantation, Director of the Judy and Bernard Briskin Center for Multiple Meyloma Research and Director of the Multiple Myeloma Program at the City of Hope Comprehensive Cancer Center.

Sutro’s novel ADCs efficiently killed multiple myeloma, mantle cell lymphoma, diffuse large B-cell lymphoma and other Non-Hodgkin lymphoma cell lines in vitro. In vivo, these ADCs significantly reduced tumor growth in ANBL-6, CAG and ARP-1 multiple myeloma models and WSU-DLCL2, OCI-Ly10, SU-DHL-6 lymphoma models.