A proof of concept for a next-generation dual conjugated combination immunostimulatory antibody-drug conjugate (IADC) was release by Sutro Biopharma, a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics.

This breakthrough concept of a tumor-targeting monotherapy, which simultaneously attacks tumor cells while stimulating a patient’s own immune system, has the promise of generating long-term immunity.

World ADC London
The IADC was generated with Sutro’s proprietary and integrated cell-free protein synthesis platform XpressCF® and site-specific conjugation platform XpressCF+™. It enables precise tumor targeting with a combination of a novel toll-like receptor (TLR) agonist and a traditional antibody-drug conjugate payload.

“This is a next-generation approach that utilizes Sutro’s technology to take ADCs into the future, potentially enabling a sustained and adaptive anti-tumor immune response,” said Sutro’s Chief Scientific Officer, Trevor Hallam, Ph.D.

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“We have showcased how a targeted cytotoxin can stimulate immunogenic cell death and provide a synergistic stimulation of immune system memory responses when paired together with TLR agonists. Generating adaptive and protective immunity from the patient’s own tumors in situ, especially in an off-the-shelf product, is a significant leap forward in targeted oncology therapeutics,” Hallam added.

Hallam was a featured speaker during the 10th Annual World ADC London where he discussed targeted immunostimulants and a promising approach to in situ immunization.

Development
To date, Sutro has designed cytokine-based immuno-oncology therapies, antibody-drug conjugates, vaccines and bispecific antibodies primarily directed at clinically-validated targets for which the current standard of care is suboptimal.

Sutro’s proprietary and integrated cell-free protein synthesis platform XpressCF® and site-specific conjugation platform, XpressCF+™, led to the discovery of STRO-001 and STRO-002, two internally-developed ADCs.

STRO-001 is a CD74-targeting ADC currently being investigated in a Phase I clinical trial of patients with advanced B-cell malignancies, including multiple myeloma and non-Hodgkin lymphoma.

STRO-002 is a folate receptor alpha (FolRα)-targeting ADC, currently being investigated in a Phase I clinical trial of patients with ovarian and endometrial cancers.

The company’s platform allows it to accelerate the discovery and development of potential first-in-class and best-in-class molecules through a rapid and systematic evaluation of protein structure-activity relationships to create optimized homogeneous product candidates.

In addition to developing its own oncology pipeline, Sutro is collaborating with select pharmaceutical and biotech companies to discover and develop novel, next-generation therapeutics. As the pace of clinical development accelerates, the company and its partners are developing therapeutics designed to more efficiently kill tumors without harming healthy cells.