The Memo: CleanMargin Bringing Real-Time Margin Assessment to Lumpectomy

Under the direction of Co-Founder and CEO Yana Reshetnyak, PhD, CleanMargin is developing a tumor-targeted fluorescence imaging agent designed to help surgeons identify cancer-positive margins in real time during breast-conserving surgery. The company’s lead agent, MarginVue, combines its proprietary pH-Low Insertion Peptide (pHLIP) technology with indocyanine green (ICG) and is being developed for use with Stryker’s SPY imaging technology. CleanMargin’s initial goal is straightforward but consequential: give surgeons information during the procedure that today may not become available until days later, potentially reducing repeat surgeries while preserving the existing pathology standard of care.

Origin Story

CleanMargin grew out of years of work on a technology designed to exploit a fundamental characteristic of solid tumors: their acidic microenvironment.

Reshetnyak helped develop pHLIP technology alongside colleagues from Yale University, the University of Rhode Island, and Memorial Sloan Kettering Cancer Center. The technology is designed to target solid tumors and ultimately became the foundation for a fluorescent imaging agent that could make cancerous tissue visible during surgery.

“I am a co-inventor of the technology and co-founder of the company,” Reshetnyak said. “We developed the fluorescent imaging agent pHLIP-ICG, brand name MarginVue, for marking tumors to visualize them during cancer fluorescence-guided surgeries. We created CleanMargin to develop the MarginVue imaging agent for approvals and commercialization.”

The U.S.-based company is initially focused on breast-conserving cancer surgery, or lumpectomy, with longer-term interest in bringing the technology to European and Asian markets. Its mission is to enable surgeons to achieve negative, or “clean,” margins during surgery, reducing the need for secondary procedures, reducing healthcare costs, and improving outcomes for women undergoing breast-conserving surgery.

The Current Landscape

The objective of a lumpectomy is to remove the cancer while preserving as much healthy breast tissue as possible. Yet surgeons currently face a significant limitation: the definitive determination of whether the margins are cancer-free comes from postoperative pathology.

Approximately 250,000 lumpectomies are performed annually in the U.S., according to Reshetnyak. In about 20% of cases, representing roughly 50,000 patients each year, pathology subsequently identifies one or more positive margins, indicating that cancer remains and that another surgery or other treatment may be required. Reshetnyak said reported positive margin rates can range from 7% to 39%, depending on surgeon experience.

“The gold standard for determining margin status currently occurs postoperatively, via pathology analysis on the resected tissue specimens,” Reshetnyak said. “Our solution is to image and determine margin status on a real-time basis during surgery, to be confirmed postoperatively via gold standard pathology analysis.”

That distinction is central to CleanMargin’s approach. Rather than replacing pathology, MarginVue is being developed to provide surgeons with additional information while there is still an opportunity to act on it.

Other FDA-approved devices and imaging approaches have been developed to address positive margins in breast cancer surgery, but Reshetnyak said cancer detection sensitivity varies from 49% to 92% and each approach carries limitations. According to Reshetnyak, there is currently no robust solution that can be easily adopted by hospitals on a broad scale.

Inside the Innovation

MarginVue combines CleanMargin’s proprietary pHLIP tumor-targeting peptide with ICG, a near-infrared fluorescent dye already used clinically for several imaging applications and widely used in operating rooms. By chemically connecting ICG to pHLIP, CleanMargin has created a new molecular entity designed to target tumors and make malignant tissue visible through fluorescence imaging.

Under CleanMargin’s approach, MarginVue is administered through a single intravenous injection two days before breast-conserving surgery. The patient then returns for surgery, where Stryker SPY technology is used to perform real-time fluorescence imaging in the operating room. Using Stryker QP software, the MarginVue fluorescence signal in the lumpectomy is set to 100%, while the signal in the margins is expressed as a percentage relative to the lumpectomy signal for the same patient.

The broader opportunity is to give surgeons actionable information before the procedure is over. Reshetnyak said the team has thus far achieved 100% sensitivity for detecting breast cancer  during surgery, with the findings subsequently confirmed by postoperative pathology.

For Reshetnyak, improving confidence in breast-conserving surgery could ultimately influence the choices available to patients.

“We believe that more women will choose lumpectomy versus mastectomy if rates of positive surgical margins and the probability of needing secondary treatments decrease,” she said.

Progress and Milestones

MarginVue is currently in a Phase II clinical trial in patients with breast cancer at Memorial Sloan Kettering Cancer Center in collaboration with Stryker Endoscopy. The trial is fully financed by a grant from the National Cancer Institute, part of the National Institutes of Health.

CleanMargin’s next objective is to complete its current Phase II work and initiate a pivotal trial to seek expedited approval for MarginVue as an imaging drug used to identify malignant lesions in adult patients with breast cancer.

In parallel, the company is raising a $5 million Series A to complete pre-commercial manufacturing. MarginVue has already been manufactured for Phase I/II clinical trials, and Reshetnyak said the lyophilized formulation has demonstrated stability exceeding five years when stored dry before reconstitution for administration.

While breast-conserving surgery represents CleanMargin’s initial focus, the underlying problem extends beyond breast cancer. Positive surgical margins remain a challenge across multiple cancer surgeries, creating a potentially broader future role for tumor-targeted intraoperative imaging.

“We do not disrupt the current standard of care,” Reshetnyak said. “Our approach of identifying positive margins during surgery is designed to eliminate or greatly reduce the risk of finding positive surgical margins in pathology after the surgery is completed.”

Join Us at LSI Europe ‘26

Reshetnyak has been selected to present at LSI Europe '26, September 28th–October 1st, in front of hundreds of global medical technology companies. Join us in welcoming her to the event in Barcelona, where she will share the latest updates on CleanMargin’s technology and development.