NEW YORK – After announcing on Tuesday that it raised CHF 1.3 million ($1.3 million) in a pre-Series A financing round, the Swiss precision oncology company PreComb Therapeutics is working to drum up more support for its functional drug testing platform, dubbed "3DTwin."
The concept of functional drug testing in precision oncology is not new. It involves creating a model of a patient's tumor cells and directly testing drugs on that model to inform treatment selection for the patient. Academic researchers and biotech startups alike have validated the approach to various degrees in blood cancers and solid tumors. The Seattle-based firm SEngine, for instance, has advanced an ex vivo organoid-based drug testing platform dubbed PARIS to guide cancer treatment including for PARP inhibitor-resistant ovarian cancer patients.
But these approaches have been limited in their feasibility and scalability, in part due to the technical requirements and expertise needed to grow the organoids and use them as drug-screening tools. That's where PreComb differentiates itself; the firm hopes to eventually offer oncologists treating any type of tumor the functional drug testing capability via a closed-system, machine learning-informed device and platform.
"The device would be pretty autonomous in that it only needs electricity," explained PreComb Cofounder and Chief Operating Officer Peter Steiner. "You can put the [tumor] sample in, put the test kit in, then run the test, and two weeks later or so you would get the result out. No user interaction required, all fully standardized and automated."
To be sure, the company has a long way to go to reach the point where it's selling closed-system functional drug testing capabilities, but based on the evolution of biomarker testing in precision oncology, Steiner has confidence that automating and scaling functional drug testing is possible.
"If you think about molecular sequencing, it only became a success on a broad scale once it was fully automated and done in machines," he said. "Our approach is to make this concept into a fully standardized, fully automated, point-of-care technology."
The first crucial step in PreComb's functional precision medicine technology involves recapitulating as many features of a patient's original tumor sample as possible. PreComb CEO and Cofounder Jens Kelm explained how it works: "We take a tissue biopsy from the tumor, dissociate the tumor, and use the whole cell population that was present in the tumor to reform microtumors."
The process of generating the microtumors takes roughly five days, Kelm said. And once the tumor twins are created, "we can use them to dose different drugs in a fully automated system to monitor the response in a similar way as the tumor response would be monitored in the clinic or in PDX models in vivo," he explained. In other words, with each drug exposed to the microtumor, the system would measure the size of the tissue and monitor its growth behavior to determine whether it responds.
According to Kelm, the microtumors include not only the features of the tumor cells themselves, but also the tumor stroma cells and the surrounding tissue, which can play a crucial role in determining patients' responses to treatment.
"Drug sensitivity is not only driven by genetics," he said. "It is also driven by the tumor microenvironment … the stroma cells, the immune components, and the immune cells."
To be sure, the molecular features are also recapitulated in the 3DTwin technology, Kelm continued.
"The beauty is that it's not an enrichment or prolongation culture, so you really have the cells that you have in the primary tumor … not an enriched population of one type of cells."
The firm is in the process of conducting a preclinical study of pancreatic cancer in animal models and is validating the technology in non-small cell lung cancer tumors produced directly from patient tumor tissue, using it as a tool to predict response to new immunological drugs. In partnership with the German Cancer Research Center, Kelm said PreComb is also testing its technology in the pediatric cancer space. "But in principle, the technology is compatible with all solid cancers," he added.
PreComb also sees the 3DTwin technology as a way to generate standardized, high-fidelity data on drug responses. "The devices will provide hundreds of drug profilers for each patient," Steiner said. "That's not something that you have at the moment in this field. … This could really build the basis for more statistical computational analysis later on. If you combine our data with all the molecular data out there and healthcare records, that would be an enormous advantage for deep data mining."
To get to the point where PreComb's systems are used on a broad enough scale to generate these data, Kelm and Steiner both acknowledged that the technology will need not only validation but also commercial approval. The firm is working toward securing the CE-IVD mark in the European Union and garnering a medical device approval in the US.
To get to this point, the firm has taken a "stepwise" approach, Steiner said, beginning with offering the technology for research use in the hopes of generating the validation data needed for regulatory approval.
"It's quite the topic at the FDA at the moment to move toward using more sophisticated means to [predict] new drug responses," he said, adding that tools like theirs could also theoretically help guide drug dosing for patients.
The clinical validation studies needed for regulatory approval are in the works, said Steiner, who predicts they could begin in about a year and a half to two years, "depending on the financing."
More funding will be needed to build, validate, and scale PreComb's technology, and the firm doesn't yet have the level of financing it needs to turn its long-term vision into a reality. "It's incredible what you can do when you have unlimited funding," he said. "The next big thing for us is the Series A financing to grow this out on a much broader scale."
The firm has also begun working with a commercial partner, though Steiner would not share the name. The hope going forward, he said, would be to attract additional pharmaceutical partners to take part in their studies "to prove that this technology can really do an enormous benefit to the research and discovery pipelines of these companies."
"A very good example of this is Foundation Medicine," said Sergey Jakimov, a managing partner and cofounder of LongeVC, a venture capital firm that participated in PreComb's pre-Series A financing round, who likened the shift toward next-generation sequencing on a broad commercial scale to what he hopes will happen with functional precision medicine. "Foundation Medicine was basically made possible because of the cost of genome sequencing going down, and because of the field accumulating a certain amount of understanding about the actionable mutations that we can transform into adjusting the treatments."
Similarly, he said, the ability to perform functional drug testing in an automated way for patients on a broad scale could generate the data needed to cyclically spur greater insight into the implications of the findings and, ultimately, greater uptake while lowering costs.
"This is why right now this is quite small and still a very boutique thing," he said. "Because it takes a lot of time and effort. We sincerely hope that PreComb will make it less boutique and more accessible."