6qclCG

Innovation: Medical imaging—molecular imaging to guide surgeons in performing complete resections of tumor tissues during operations
Targeted Cancer(s): Breast cancer
Scientific Leadership: James Basilion, Ph.D.; Matthew Bogyo, Ph.D.
Stage of Project: Formulation nearly completed; pharmacokinetic and toxicokinetic (PK/TOX) reports soon underway; clinic-ready thereafter, assuming continued positive results

6qcICG is a smart, quenched, substrate-based probe which targets cancer-associated, activated cysteine cathepsins. Cysteine cathepsins are associated with cancer growth and metastasis, and they are preferentially-expressed in the margins of more than 80% of solid-tumor cancers. The agent is uniquely flexible—and can be administered in-vivo systemically, in-vivo topically and ex-vivo topically. The probe is highly selective and remains optically silent until it encounters cancer tissue. When it detects cancer, 6qcICG robustly activates in minutes, making it ideally-suited to intraoperative cancer tissue and margin assessment.

• The challenge for surgeons is that it is very difficult to determine where cancer ends and healthy tissue begins. Complete surgical resections of solid cancers would produce dramatically higher cure rates, and technology enabling surgeons to assess the status of tumor margins while in the operating room would save tremendously in healthcare costs.
• Breast, colon, prostate and lung are among the most common solid cancers—and the largest contributors to cancer mortality. Complete resection failure for these cancers runs from 7% to 85%.
• The cancer surgery market is large and growing. Annually, more than four million surgical procedures could benefit from an enhanced cancer margin identification technology.
• The first target is for breast cancer lumpectomies, for which the repeat procedure rate due to incomplete resection averages nearly 25%.

• Current technologies for intra-operative assessment of tumor margin infiltrates (e.g., cytology and frozen section) have significant problems and have not proven robust enough for widespread clinical adoption.
• By targeting only those enzymes that have significantly-increased activity in breast cancer tumors (and especially in active tumor margins), 6qcICG can provide reliable intra-operative detection of residual disease after resection in breast tumor margins, enabling complete excision of diseased tissue in a single surgery.
• 6qcICG is a quenched probe and is activated only by cancer-associated enzymes. It is not activated by healthy tissue.
• Unlike other molecular probes, which require the systemic administration of large amounts of probe hours or days before surgery, 6QcICG requires the intra-operative topical application of minute amounts of probe into the surgical cavity. The probe activates within minutes, precisely delineating any remaining cancer tissues.
• Even with multiple applications, total dosage will likely fall in the microdose range enabling a more direct and less expensive path to patient trials.

• Formulation: Fifty different blends of poloxamer gels have been tested and the best candidate selected; in the most optimal formulation of 6qcNIR probe and gel, the formula is liquid at room temperature and has high viscosity at body temperature, and initial tests with in-vivo topical application in animal models show high promise with excellent probe retention and a good activation profile in the surgical cavity
• Proof of Concept: Statistically-significant sensitivity and specificity data, both in the 90^th percentile, are already in hand for 6qcNIR using human tumors and excised xenografts using the probe ex-vivo; if duplicated in-vivo, repeat surgery rates in breast conservation surgery could be reduced by up to 90%
• Intellectual Property: Patents are owned or licensed internally, and others are underway; know-how is similarly in-house
• Clinical Development Plan: As final formulation wraps up, the regulatory submission process will commence, including production of key PK/TOX reports; if successful, Phase 1a clinical studies in healthy volunteers and a Phase 1b trial in breast cancer patients will begin