By Nuala Moran, Europe Editor
Originally published May 15, 2025, in BioWorld

Newco Avidicure NV arrived on the scene with a hefty $50 million in seed funding to advance novel antibody formats the company says will surpass the best qualities of first-generation antibodies, checkpoint inhibitors, T-cell engagers and antibody-drug conjugates.

If that is a large claim, Avidicure’s founders have decades of experience in engineering antibodies. They have now applied this expertise to design constructs which are dual agonists that target tumor-specific receptors, while being affinity-engineered so they are functional only when in contact with a cancer cell.

These constructs, which Avidicure calls AVC-Boosters, have been shown to unlock strong and orchestrated immune responses across the innate and adaptive immune system.

“It really is unlike any other modality out there and, in a way, that is a surprise because it’s so logical what we have done,” said Arthur Lahr, CEO. “What we have is a normal IgG [antibody] that has two genetically fused domains, so it has a dual agonistic mechanism, and we’ve not increased, but [rather] reduced the affinity of both of these additional binders,” he told BioWorld.

As Lahr noted, most antibody-like constructs, for example, T-cell engagers, natural killer engagers, antibody-drug conjugates and checkpoint inhibitors, typically have one arm binding to a tumor and one binding to an immune cell, and activate one pathway in the immune system.

With T-cell engagers, this works well – in fact, too well, Lahr said. “You get a very strong killing, actually too strong, because they trigger CD3, which is a very strong activator.”

Meanwhile, to date, NK engagers have shown modest effects because they bind to CD16, which is a weak activator. Despite attempts to increase potency by adding a co-stimulatory domain, or a cytokine, “you still don’t get the full effect,” said Lahr. “You just know, from basic biology as well as from CAR T experience, that you really need to trigger multiple signals into an immune cell, to get them to properly expand and be activated, and also to be safely activated.”

While the need to build in an array of activation signals and trigger different pathways is recognized in CAR T-cell therapy, no one has translated that insight to engineer antibodies that activate multiple immune pathways, Lahr noted.

At the same time, it is necessary to do this safely, hence the need for avidity engineering. “You need to make sure these two additional binders don’t overactivate the immune system. So you actually have to reduce the affinity of these binders, in order to make the full construct function,” Lahr said. Specifically, the domains are engineered to only be functional within the immunological synapse that is formed between immune cells and the targeted tumor cells.

The tumor-specific targeting means there is a very high local concentration of the antibodies. As a result – and despite the fact that the binders are low affinity – there is antibody-dependent cellular toxicity, prompting immune cells to kill cancer cells that are coated in antibodies.

As Lahr acknowledges, an antibody is very different from a CAR T, and the challenge now is to make the CAR T approach to triggering multiple immune pathways work in a different modality.

Preclinical research that was presented at the American Association of Cancer Research meeting last month, showed Avidicure’s antibodies were highly effective in stimulating immune cells in patient tissue and in mice. That significantly improved tumor control and turned cold tumors hot.

AVC-boosters were seen to activate multiple cytotoxic and interferon gamma pathways, to stimulate CD8+ T-cell activation, to downregulate pro-tumor pathways in regulatory T cells and to induce a shift in macrophages from the immunosuppressive M2 to the pro-inflammatory M1 phenotype.

Armed with the seed funding, Amsterdam, the Netherlands-based Avidicure will now take forward the lead product, AVC-S-101, a TROP2-targeting booster that is being developed for non-small-cell lung cancer and other indications. IND-enabling work has started with the aim of entering the clinic around the end of 2026. The company also has HER2- and EGFR-targeting products in the pipeline, and has data showing the booster concept works in these two cases.

Alongside Lahr, the founding management team consists of Dirk De Naeyer, chief operating officer; Robert Friesen, chief scientific officer; and Govert Schouten, chief business officer. All were previously executives in the European biotechs such as Crucell, Ablynx and Kiadis. Together, “we created the technology completely from scratch ourselves,” said Lahr.

The $50 million seed round was led by EQT Life Sciences with participation from Kurma Partners, Biogeneration Ventures, BOM, Curie Capital and V-Bio Ventures.

The funding is “enough to hit some very valuable milestones,” Lahr said, adding, “We have multiple options to expand our cash and our cash runway that we’re currently pursuing.”

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