Sutro Biopharma confirmed that the U.S. Food and Drug Administration (FDA) has concluded their 30-day review of the Investigational New Drug (IND) application for STRO-002 to be evaluated in a Phase I clinical study as a potential treatment for ovarian and endometrial cancer.

STRO-002 is an antibody-drug conjugate or ADC targeting folate receptor-α, a cell-surface protein expressed in 80% of gynecological cancers, including ovarian and endometrial cancers.

The investigational drug was developed using Sutro’s proprietary cell-free protein synthesis and site-specific conjugation platform, XpressCF+™, which enables precise design, rapid empirical optimization, and manufacture of site-specific ADCs.

MabPlex
 
Photo 1.0. William Newell, chief executive officer of Sutro Biopharma: “The Phase I clinical trial of STRO-002 is expected to begin in early 2019 with the goal to investigate the safety, tolerability and preliminary anti-tumor activity of STRO-002 in patients with gynecologic malignancies.”

In contrast to first-generation commercially available ADCs that comprise a mixture of imprecisely conjugated antibodies, Sutro’s proprietary and integrated cell-free protein synthesis and site-specific conjugation platform, XpressCF+™, led to the discovery of STRO-001 and STRO-002, and results in highly optimized ADCs comprising a single molecular species.

STRO-001 is a first-in-class ADC targeting CD74, a protein highly expressed in multiple myeloma and non-Hodgkin’s lymphoma, and is currently in a Phase I study.

STRO-002, , has been engineered to use Sutro’s novel, proprietary SC239 linker-payload, designed for increased stability and potency, which results in effective targeting of cancer cells and precise delivery of the payload.

Milestone
“The ability to begin our Phase I clinical study marks an important milestone that expands Sutro’s clinical development pipeline and further validates our technology for the design of unique and potent antibody-drug conjugates,” said Bill Newell, Sutro’s Chief Executive Officer.

“The Phase I clinical trial of STRO-002 is expected to begin in early 2019 with the goal to investigate the safety, tolerability and preliminary anti-tumor activity of STRO-002 in patients with gynecologic malignancies,” Newell added.

Clinical trial
Patients with ovarian cancer will be enrolled during the dose escalation-phase of the study, and two separate cohorts for ovarian and endometrial cancer will be evaluated during dose expansion.

“Ovarian and endometrial cancer patients need targeted treatment options with better tolerability and efficacy,” noted Wendel Naumann, MD, a Gynecologic Oncologist Professor, at the Levine Cancer Institute, Carolinas Medical Center.

Preclinical development
In preclinical studies, STRO-002 effectively delivered its cytotoxin to targeted cancer cells without significant accumulation of a toxic metabolite in the blood. Testing of clinically relevant doses in non-human primates showed no evidence of ocular toxicity, a vexing problem associated with conventional ADCs containing standard tubulin-inhibiting agents.

“This is an important development for ADC-based cancer therapeutics and could provide new means to achieving greater anti-tumor activity in the clinic before the onset of dose-limiting side effects,” added Arturo Molina, MD, Sutro’s Chief Medical Officer.

Unlike first-generation ADCs, STRO-002 is a homogeneous, site-specific antibody-drug conjugate that incorporates a novel, proprietary linker-warhead, thereby enabling effective and precise payload delivery to targeted cancer cells. Preclinical studies demonstrated efficacy of STRO-002’s potent in vitro cytotoxicity in ovarian and endometrial cancer cell lines, and tumor growth inhibition in multiple in vivo ovarian and endometrial cancer models.

Safety studies conducted in non-human primates have shown tolerability at clinically relevant doses with no observed ocular toxicity.