PQ203 Receives Regulatory Clearance for Breast Cancer Trial

Regulatory agencies in the United States and Canada have granted clearance for a phase 1 clinical trial of PQ203, a novel peptide drug conjugate, in patients with advanced triple-negative breast cancer (TNBC), and the US FDA has granted the agent fast track designation.¹

The investigational therapy, developed by ProteinQure uses a proprietary platform that combines physics-based modeling and generative machine learning. The fast track designation is intended to expedite the development and review of drugs for serious conditions that address an unmet medical need, underscoring the potential of PQ203 to offer a new therapeutic option for this aggressive subtype of breast cancer.

“This is a major step forward for ProteinQure and for the field of rationally designed peptide therapeutics,” said Dave Garman, vice president of Translation and Development at ProteinQure, in a press release. “The fast track designation reflects the FDA’s recognition of the promise PQ203 holds for cancer patients, and we are thrilled to move swiftly into the clinic across North America.”

TNBC, which accounts for approximately 10 to 15% of all breast cancers, is characterized by its lack of expression of estrogen receptor, progesterone receptor, and HER2. This absence of standard targets makes it particularly difficult to treat and is associated with a higher risk of recurrence and metastasis compared to other breast cancer subtypes. The current standard of care often involves a combination of surgery, radiation, and chemotherapy, with newer therapies like sacituzumab govitecan (Trodelvy) providing a key advance. However, resistance to these therapies remains a significant challenge, highlighting the need for novel agents with different mechanisms of action.

PQ203 is designed to target the Sortilin receptor, a protein that is highly expressed in TNBC tumor tissue. The drug is a first-in-class therapeutic that functions as a peptide drug conjugate, delivering a cytotoxic payload directly to cancer cells that express the Sortilin receptor.² Preclinical data cited by ProteinQure, which includes efficacy in patient-derived xenograft models, showed that PQ203 was effective even in models that had developed resistance to sacituzumab govitecan, suggesting a potential role for the drug in overcoming existing treatment resistance.

The upcoming phase 1 trial will be conducted in both the US and Canada. The study will employ an accelerated titration design, a methodology intended to safely and efficiently determine the optimal dose and schedule of PQ203.¹ This design allows for more rapid dose escalation in the initial stages of the trial, provided no dose-limiting toxicities are observed.

The primary objectives of the trial are to evaluate the safety and tolerability of the drug, as well as to characterize its pharmacokinetics and pharmacodynamics. The study will also assess the anticancer activity of PQ203, providing initial insights into its clinical efficacy. The first clinical site to open will be the Princess Margaret Cancer Centre in Toronto, with plans to expand to additional sites in the US.

REFERENCES:

1. ProteinQure Receives Regulatory Clearance to Initiate Phase I Trial for PQ203 in the U.S. and Canada; Granted FDA Fast Track Designation. News release. ProteinQure. August 7, 2025. Accessed August 8, 2025. https://tinyurl.com/3n3v6a2z

2. Science. ProteinQure. Accessed August 8, 2025. https://www.proteinqure.com/science/