LONDON – A founding father of anti-angiogenesis therapy, Peter Carmeliet is turning his previous work on its head in new research which indicates that rather than destroying tumor vasculature, it should be piggy-backed as a means to recruit immune cells to a tumor.
Those insights form the basis for newco Montis Biosciences, which has spun out of Carmeliet’s lab at Katholieke Universiteit Leuven, Belgium, with €8.4 million (US$9 million) in seed funding. That will enable the company to validate targets involved in interactions between the endothelial cells lining blood vessels and perivascular macrophages, through which the influx of immune cells into tumors is regulated.
Carmeliet said it is becoming increasingly clear that endothelial cells in tumor vasculature play a major role in how the immune system reacts to cancer, and that the interplay between endothelial cells and perivascular macrophages shapes that response.
“Historical therapies targeting the tumor vasculature largely ignored this role and instead destroyed the vessels to starve the tumor,” Carmeliet said. “Our research is showing that rather than destroying blood vessels, we can use them to herd the correct immune cells to the tumor and to get much more potent and sustained effects.”
Carmeliet has spent more than 25 years painstakingly studying the molecular mechanisms involved in angiogenesis and uncovering their influence on health and disease. His work underlies a number of anti-angiogenesis therapies. The change in approach to preserving tumor blood supply builds on single cell transcriptomic studies, through which it has become possible to investigate communications between immune cells and the tumor vasculature.
Montis has intellectual property based on how those two classes of cells interact, and which it says can be modulated to allow immune cells into a tumor, with the aim of restoring immunogenicity.
“It is still very early; this is a very novel concept,” said Luc Dochez, CEO of Leuven-based Montis. “There is no lead molecule, but we have a couple of targets being validated as we speak,” he told BioWorld.
Montis references two papers by Carmeliet and the company’s scientific co-founder Massimiliano Mazzone, head the Laboratory of Tumor Inflammation and Angiogenesis at KU Leuven, describing the use of transcriptomics to explore how immune-related functions of endothelial cells work in concert with perivascular macrophages.
“We think single cell transcriptomics is a very powerful tool; it leads to novel targets and insights,” Dochez said. “But you’ve got to functionally validate, you’ve got to interpret the data, and that’s what we are doing now.”
The two published studies are in breast and lung cancers. However, said Dochez, “the idea is [the technology] would be more broadly applicable. [The researchers] had access to these tumor samples, but clearly we think it can be applied to other tumors,” he said.
In lung cancer, Carmeliet, Mazzone and colleagues conducted single-cell RNA sequencing of 56,771 endothelial cells from human and mouse tumors. That detected 16 previously unknown phenotypes, including identifying cells that express immunoregulatory gene signatures.
The seed financing will allow Montis to prioritize targets, with Dochez saying, “We will definitely have proof of concept and a number of validated targets, and start hit-to-lead. Whether we have a lead molecule will remain to be seen.” He said he expects the molecules to be antibodies, but it depends “on what else pops up” during target validation.
Its seed round of €8.5 million is sizeable for a European startup, and Montis also has attracted a solid band of venture capital backers, led by the specialist oncology fund Droia Ventures. Other investors are Pfizer Ventures, Polaris Partners, of Waltham, Mass., and London-based Alsa Ventures.
“It’s not as big as some launch rounds in the U.S., where people may be raising $20 to $40 million, but it is what is needed to bring great academic IP into a solid base on which to build a company. We will get to meaningful milestones to do a larger series A,” Dochez said.
Droia had a big payday in October 2018, when it sold another immmuno-oncology specialist, Tusk Therapeutics Ltd., to Roche Holdings AG for a potential $760 million. Of that, $81 million was paid up front, for a company with a single product, which at that stage was still in preclinical development.
Dochez, who was CEO of Tusk at the point of acquisition, said it is “hard to predict” if there will be a similarly early exit from Montis. “We’ve got to create optionality …. And at every inflection point make a decision on how to proceed. There’s no fixed strategy,” he said.