NEW YORK – Startup Droplet Biosciences has thrown its hat in the liquid biopsy ring, advancing a strategy that uses lymphatic fluid instead of blood plasma as a source for detecting cancer-associated DNA alterations.
Founded in 2021, the company has been quiet on its plans thus far, but said on Thursday that it recently received an $8 million seed investment from MIT venture capital spinout The Engine to continue establishing proof of concept for its technology.
Droplet CEO Theresa Tribble said that the company's foundational breakthrough is a noninvasive process to access lymph via surgical drain fluid after tumor resection surgery, which can be tested for minimal residual disease (MRD). The approach doesn't stray far from existing blood-based MRD technologies in terms of molecular targets or genomic sequencing, but rather does in its sampling strategy.
While there has long been evidence that the lymphatic system plays a critical role in cancer metastasis, it hasn't presented the same easy target as blood, Tribble said, because it hasn't been viewed as being as easily or reliably sampled.
The first application that the firm is pursuing with its surgical drain approach is detecting residual disease in head and neck cancer patients immediately after surgery, using a strategy developed by Jose Zevallos, chair of otolaryngology at the University of Pittsburgh, and Aadel Chaudhuri, assistant professor of cancer biology, radiation oncology, genetics, computer science, and biomedical engineering at Washington University in St. Louis, both listed as scientific cofounders of the new company.
"[Zevallos'] insight was that every time he takes a tumor out, he places a surgical drain. And that surgical drain is the source of really interesting information — ctDNA, proteins, immune cells — it's all relevant to how you might either identify minimal residual disease or predict patient care [needs]," Tribble said.
Zevallos and Chaudhuri then met Stan Lapidus, Droplet's fourth cofounder, who introduced the two to Tribble and The Engine. Droplet CSO Wendy Winckler joined about six months ago and has been tasked with accelerating the company's progress toward a clinical product for the head and neck cancer space.
"We've been developing a ctDNA approach using this fluid that is much closer to the tumor and as such, is more concentrated for ctDNA when there is residual cancer," Winckler said. "We have demonstrated an initial proof of concept and we're looking forward to taking that into clinical tests over the next year or so," she added.
In blood-based liquid biopsy, MRD strategies include patient-specific mutation detection methods, like Natera's tumor-informed Signatera assays, and methylation-based tumor-naive products such as Guardant Health's Reveal test.
Winckler said that Droplet has the option to do both, adding that the firm's biggest differentiation from existing MRD isn't in the type of signal it's detecting, but in the significantly improved sensitivity that lymphatic fluid offers.
"That's really the challenge of blood-based MRD tests today, that there simply aren't that many tumor genome copies circulating in the blood in a setting where you have already removed most of the tumor. So if you take a 10-ml blood draw, you may not capture those genomes, even if you know you have a really sensitive [sequencing] method," Winckler said.
"We're closer to the tumor so we have more copies of DNA, and we've shown that we have more sensitivity there compared to blood samples. So that's translating into superior performance in being able to predict recurrence," she added.
Droplet hasn't published this comparative performance data, so many questions remain about that boost to sensitivity and how it may or may not correspond with improved clinical outcomes.
Winckler and Tribble said that the firm is working on an abstract for presentation at an upcoming oncology conference. Chaudhuri and Zevallos also have a paper in revision describing their work developing the surgical drain-based method in human papillomavirus-positive head and neck cancer.
According to Winckler, a second differentiation point is timing. Access to surgical drain fluid starts immediately after surgery, and thus, identification of residual disease via circulating tumor DNA could be virtually immediate.
Investigators have also used blood-based MRD assays at immediate post-surgery time points, but in clinical use, tests are usually performed beginning several weeks after surgery because clinical studies have established that this offers the best chance of detection.
Testing within 24 hours of surgery, Droplet would potentially be able return results before a patient and their caregiver make initial adjuvant therapy decisions, Winckler said.
She also said there is a wide field of potential indications for Droplet's technology outside of head and neck cancer. Although only about half of solid tumor surgeries involve the placement of a drain, this doesn't necessarily limit the application of Droplet's approach to that 50 percent of patients, she argued.
In breast cancer, for example, patients undergoing mastectomy will typically have a drain placed, while those having a lumpectomy will most likely not. However, even for individuals undergoing lumpectomy, physicians often drain lymphatic fluid at a two-to-three-week postoperative visit.
More broadly, Winckler said that Droplet believes there are multiple ways to access lymphatic fluid outside of the surgical setting.
"Our thought is that we start [in cancers] where drains are routinely placed so that we don't have to change clinical practice to collect fluid in a new way," she said. "Then as we demonstrate the power of this fluid and the information that comes from it to direct patient care and save lives, I think we'll be able to move in that direction and introduce new ways to collect fluid over time."
Droplet's lead product will be in head and neck cancer, which uses a subcutaneous drain after surgery, but the company sees a clear path forward in cancers that feature two other drain types — abdominal and thoracic.
Winckler said that Droplet's product development will benefit from the fact that blood-based MRD technologies are already well established, both scientifically and, more recently, clinically.
"We simply have a superior fluid that has a higher concentration of the targets we are after," she said.
Tribble said the firm plans to initially launch its head and neck cancer assay as a laboratory-developed test, and will consider a US Food and Drug Administration submission "down the road."
"We want to focus in the early days on developing clinical utility data that demonstrates to both clinicians and to payors that our approach is beneficial to patients," she said. In this regard, the fact that blood-based techniques have already gained clinical traction is also a boon.
Droplet believes its technology could also have numerous applications beyond MRD. "This fluid hasn't been explored deeply by existing diagnostics players, and we are also generating interesting data regarding markers that are likely localized and important, proteins and specific cells that give us additional potential product lines in addition to MRD," Tribble said.
"That's actually some of the newest data we have generated … because we are specifically in the space where metastasis is occurring, where those cells are beginning to grow and migrate," Winckler added. "I think that we're seeing some really interesting signals about how metastasis is occurring, as well as how the host immune response to those tumors is occurring."